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Chen KJ, Chuang CY, Lien MY, Su CW, Chen MYC, Tsai HC, Yang SF, Tang CH. Genetic associations of Neat1 polymorphisms with clinicopathologic characteristics of tongue cancer. Int J Med Sci 2025; 22:1208-1214. [PMID: 40027195 PMCID: PMC11866524 DOI: 10.7150/ijms.103842] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Accepted: 01/23/2025] [Indexed: 03/05/2025] Open
Abstract
One of the most common malignant tumors of the head and neck region is tongue cancer. Long noncoding RNAs (lncRNAs) called nuclear enriched abundant transcript 1 (Neat1) are linked to tumor growth, survival, and apoptosis in a variety of cancer types; however, it is unclear how these factors relate to tongue cancer. Furthermore, it is unknown how Neat1 polymorphisms and clinicopathological traits in individuals with tongue cancer relate to one another. We looked examined the effects of three variants in the Neat1 gene and clinicopathological characteristics on the risk of tongue cancer in 400 male Taiwanese patients who already had the disease. Carriers of the CT+TT heterozygote of SNP rs3825071 were at a significantly lower risk to clinical stage (III+IV) and lymph node metastasis compared to those with the CC genotype. For non-smoking tongue cancer patients, but not those who smoke, the SNP rs3825071 was associated with a lower clinical stage (III+IV) and reduced lymph node metastasis. The Cancer Genome Atlas database noted that Neat1 mRNA levels are higher in tongue cancer patients compared to normal tissues and are associated with tumor stage and metastasis. This study is the first to establish a link between the clinicopathological features of tongue cancer patients and Neat1 polymorphisms.
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Affiliation(s)
- Kwei-Jing Chen
- School of Dentistry, China Medical University, Taichung, Taiwan
- Department of Dentistry, China Medical University Hospital, Taichung, Taiwan
| | - Chun-Yi Chuang
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Department of Otolaryngology, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Ming-Yu Lien
- School of Medicine, China Medical University, Taichung, Taiwan
- Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chun-Wen Su
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Michael Yuan-Chien Chen
- School of Dentistry, China Medical University, Taichung, Taiwan
- Department of Dentistry, China Medical University Hospital, Taichung, Taiwan
| | - Hsiao-Chi Tsai
- Department of Medicine Research, China Medical University Beigang Hospital, Yunlin, Taiwan
| | - Shun-Fa Yang
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Chih-Hsin Tang
- School of Medicine, China Medical University, Taichung, Taiwan
- Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan
- Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung, Taiwan
- Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
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Tang D, Wang H, Jiang Y, Chen M, Zhang G, Wu S, Wang Y. ATRA-induced NEAT1 upregulation promotes autophagy during APL cell granulocytic differentiation. PLoS One 2024; 19:e0316109. [PMID: 39715205 DOI: 10.1371/journal.pone.0316109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2024] [Accepted: 12/05/2024] [Indexed: 12/25/2024] Open
Abstract
AIMS Acute promyelocytic leukemia (APL) progresses quickly and often leads to early hemorrhagic death. Treatment with all-trans retinoic acid (ATRA) promotes differentiation of APL cells and clinical remission, making APL a potentially curable malignancy. Understanding how ATRA works may lead to new treatments for other types of leukemia. Long non-coding RNA NEAT1 has been implicated in the differentiation of APL cells. This study aims to elucidate the specific role of NEAT1 in the granulocytic differentiation of APL. METHODS The influence of NEAT1 on autophagy and PML/RARα degradation was assessed using western blot assays. The impact of NEAT1 on the expression of autophagy-related genes was evaluated through quantitative real-time RT-PCR. Mechanistic insights into the role of NEAT1 in modulating autophagy were supported by RNA immunoprecipitation and RNA pulldown assays. KEY FINDINGS Knockdown of NEAT1 suppressed autophagy and attenuated ATRA-induced PML/RARα degradation and granulocytic differentiation of APL cells. Subsequent screening of autophagy-related genes demonstrated that silencing NEAT1 impaired the ATRA-induced upregulation of ATG10 and ATG12. Mechanistic investigations revealed that the RNA-binding protein TAF15 interacted with NEAT1, synergistically stabilizing the mRNA of ATG10 and ATG12. Furthermore, knockdown of NEAT1 impaired the interactions between TAF15 and the mRNAs of ATG10 and ATG12, thereby compromising their mRNA stability. SIGNIFICANCE Our study elucidates the critical role of NEAT1-mediated autophagy in the differentiation of APL cells and delineates the molecular mechanism by which upregulation of NEAT1 enhances autophagy. Specifically, NEAT1 binds to the RNA-binding protein TAF15, which in turn stabilizes the mRNA of both ATG10 and ATG12.
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MESH Headings
- Humans
- Autophagy/drug effects
- Leukemia, Promyelocytic, Acute/metabolism
- Leukemia, Promyelocytic, Acute/pathology
- Leukemia, Promyelocytic, Acute/genetics
- RNA, Long Noncoding/genetics
- RNA, Long Noncoding/metabolism
- Cell Differentiation/drug effects
- Tretinoin/pharmacology
- Up-Regulation/drug effects
- Cell Line, Tumor
- Granulocytes/metabolism
- Granulocytes/drug effects
- Oncogene Proteins, Fusion/metabolism
- Oncogene Proteins, Fusion/genetics
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Affiliation(s)
- Doudou Tang
- Department of Respiratory and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Hunan Centre for Evidence-based Medicine, Central South University, Changsha, Hunan, China
| | - Huihui Wang
- Department of Hematology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Institute of Molecular Hematology, Central South University, Changsha, Hunan, China
| | - Yafeng Jiang
- Department of Hematology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Mingjie Chen
- Shanghai NewCore Biotechnology Co., Ltd., Minhang District, Shanghai, China
| | - Guangsen Zhang
- Department of Hematology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Institute of Molecular Hematology, Central South University, Changsha, Hunan, China
| | - Shangjie Wu
- Department of Respiratory and Critical Care Medicine, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Hunan Centre for Evidence-based Medicine, Central South University, Changsha, Hunan, China
| | - Yewei Wang
- Department of Hematology, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
- Institute of Molecular Hematology, Central South University, Changsha, Hunan, China
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Jin X, Huang CX, Tian Y. The multifaceted perspectives on the regulation of lncRNAs in hepatocellular carcinoma ferroptosis: from bench-to-bedside. Clin Exp Med 2024; 24:146. [PMID: 38960924 PMCID: PMC11222271 DOI: 10.1007/s10238-024-01418-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2024] [Accepted: 06/24/2024] [Indexed: 07/05/2024]
Abstract
Despite being characterized by high malignancy, high morbidity, and low survival rates, the underlying mechanism of hepatocellular carcinoma (HCC) has not been fully elucidated. Ferroptosis, a non-apoptotic form of regulated cell death, possesses distinct morphological, biochemical, and genetic characteristics compared to other types of cell death. Dysregulated actions within the molecular network that regulates ferroptosis have been identified as significant contributors to the progression of HCC. Long non-coding RNAs (lncRNAs) have emerged as influential contributors to diverse cellular processes, regulating gene function and expression through multiple mechanistic pathways. An increasing body of evidence indicates that deregulated lncRNAs are implicated in regulating malignant events such as cell proliferation, growth, invasion, and metabolism by influencing ferroptosis in HCC. Therefore, elucidating the inherent role of ferroptosis and the modulatory functions of lncRNAs on ferroptosis in HCC might promote the development of novel therapeutic interventions for this disease. This review provides a succinct overview of the roles of ferroptosis and ferroptosis-related lncRNAs in HCC progression and treatment, aiming to drive the development of promising therapeutic targets and biomarkers for HCC patients.
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Affiliation(s)
- Xin Jin
- Department of Gastroenterology and Hepatology, Fengdu People's Hospital, Fengdu County, Chongqing, 408200, China
| | - Chun Xia Huang
- Department of Gastroenterology and Hepatology, Fengdu People's Hospital, Fengdu County, Chongqing, 408200, China
| | - Yue Tian
- Department of Gastroenterology and Hepatology, Fengdu People's Hospital, Fengdu County, Chongqing, 408200, China.
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Sha Y, Liu X, Yan W, Wang M, Li H, Jiang S, Wang S, Ren Y, Zhang K, Yin R. Long Non-Coding RNA Analysis: Severe Pathogenicity in Chicken Embryonic Visceral Tissues Infected with Highly Virulent Newcastle Disease Virus-A Comparison to the Avirulent Vaccine Virus. Microorganisms 2024; 12:971. [PMID: 38792800 PMCID: PMC11123907 DOI: 10.3390/microorganisms12050971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 04/12/2024] [Accepted: 05/09/2024] [Indexed: 05/26/2024] Open
Abstract
There are significant variations in pathogenicity among different virulent strains of the Newcastle disease virus (NDV). Virulent NDV typically induces severe pathological changes and high mortality rates in infected birds, while avirulent NDV usually results in asymptomatic infection. Currently, the understanding of the specific mechanisms underlying the differences in host pathological responses and symptoms caused by various virulent NDV strains remains limited. Long non-coding RNA (lncRNA) can participate in a range of biological processes and plays a crucial role in viral infection and replication. Therefore, this study employed RNA-Seq to investigate the transcriptional profiles of chicken embryos' visceral tissues (CEVTs) infected with either the virulent NA-1 strain or avirulent LaSota strain at 24 hpi and 36 hpi. Using bioinformatic methods, we obtained a total of 2532 lncRNAs, of which there were 52 and 85 differentially expressed lncRNAs at 24 hpi and 36 hpi, respectively. LncRNA analysis revealed that the severe pathological changes and symptoms induced by virulent NDV infection may be partially attributed to related target genes, regulated by differentially expressed lncRNAs such as MSTRG.1545.5, MSTRG.14601.6, MSTRG.7150.1, and MSTRG.4481.1. Taken together, these findings suggest that virulent NDV infection exploits the host's metabolic resources and exerts an influence on the host's metabolic processes, accompanied by excessive activation of the immune response. This impacts the growth and development of each system of CEVTs, breaches the blood-brain barrier, inflicts severe damage on the nervous system, and induces significant lesions. These observations may be attributed to variations in pathology. Consequently, novel insights were obtained into the intricate regulatory mechanisms governing NDV and host interactions. This will aid in unraveling the molecular mechanisms underlying both virulent and avirulent forms of NDV infection.
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Affiliation(s)
- Yuxin Sha
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun 130062, China; (Y.S.); (X.L.); (W.Y.); (M.W.); (H.L.); (S.J.); (S.W.); (Y.R.); (K.Z.)
| | - Xinxin Liu
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun 130062, China; (Y.S.); (X.L.); (W.Y.); (M.W.); (H.L.); (S.J.); (S.W.); (Y.R.); (K.Z.)
- College of Food Science and Engineering, Jilin University, Changchun 130062, China
| | - Weiwen Yan
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun 130062, China; (Y.S.); (X.L.); (W.Y.); (M.W.); (H.L.); (S.J.); (S.W.); (Y.R.); (K.Z.)
| | - Mengjun Wang
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun 130062, China; (Y.S.); (X.L.); (W.Y.); (M.W.); (H.L.); (S.J.); (S.W.); (Y.R.); (K.Z.)
| | - Hongjin Li
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun 130062, China; (Y.S.); (X.L.); (W.Y.); (M.W.); (H.L.); (S.J.); (S.W.); (Y.R.); (K.Z.)
| | - Shanshan Jiang
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun 130062, China; (Y.S.); (X.L.); (W.Y.); (M.W.); (H.L.); (S.J.); (S.W.); (Y.R.); (K.Z.)
| | - Sijie Wang
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun 130062, China; (Y.S.); (X.L.); (W.Y.); (M.W.); (H.L.); (S.J.); (S.W.); (Y.R.); (K.Z.)
| | - Yongning Ren
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun 130062, China; (Y.S.); (X.L.); (W.Y.); (M.W.); (H.L.); (S.J.); (S.W.); (Y.R.); (K.Z.)
| | - Kexin Zhang
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun 130062, China; (Y.S.); (X.L.); (W.Y.); (M.W.); (H.L.); (S.J.); (S.W.); (Y.R.); (K.Z.)
| | - Renfu Yin
- State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Key Laboratory of Zoonosis Research, Ministry of Education, Department of Preventive Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun 130062, China; (Y.S.); (X.L.); (W.Y.); (M.W.); (H.L.); (S.J.); (S.W.); (Y.R.); (K.Z.)
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5
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Dong Y, Hu M, Tan K, Dai R. ZNF143 inhibits hepatocyte mitophagy and promotes non-alcoholic fatty liver disease by targeting increased lncRNA NEAT1 expression to activate ROCK2 pathway. Epigenetics 2023; 18:2239592. [PMID: 37566742 PMCID: PMC10424604 DOI: 10.1080/15592294.2023.2239592] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2023] [Revised: 05/04/2023] [Accepted: 05/16/2023] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the most common hepatic disorders worldwide. The mitophagy is suggested to be repressed in NAFLD, but the mechanism remains to be elucidated. METHODS NAFLD cell and mouse models were established by treating with free fatty acid (FFA) and feeding a high fat diet (HFD), respectively. QRT-PCR, Western blotting, or IHC measured the expression of ZNF143, lncRNA NEAT1, ROCK2, and lipid formation/mitophagy-related proteins. Cell viability and mitophagy were evaluated by MTT and immunofluorescence. The chloroform-methanol extraction method measured triglyceride and total cholesterol levels. ELISA detected ALT and AST levels. The interactions among ZNF143, lncRNA NEAT1 and SND1 were analysed by ChIP, dual-luciferase reporter, pull-down, and RIP. The lipid droplets were determined by Oil-red O and HE staining. RESULTS ZNF143 and lncRNA NEAT1 were upregulated in hepatic cells treated with FFA (p < 0.01 and p < 0.001). Knockdown of ZNF143 or lncRNA NEAT1 inhibited lipid droplets formation, while promoting mitophagy (p < 0.01 and p < 0.001). ZNF143 promoted lncRNA NEAT1 transcriptional expression through binding to its promoter. LncRNA NEAT1 increased ROCK2 mRNA stability by targeting SND1. LncRNA NEAT1 or ROCK2 overexpression reversed the effect of ZNF143 or lncRNA NEAT1 knockdown on hepatic steatosis and mitophagy (p < 0.01 and p < 0.001). ZNF143 or lncRNA NEAT1 knockdown inhibited HFD-induced steatosis and promoted mitophagy in vivo (p < 0.01 and p < 0.001). CONCLUSION The upregulation of lncRNA NEAT1 caused by ZNF143 promoted NAFLD through inhibiting mitophagy via activating ROCK2 pathway by targeting SND1, providing potential targets for NAFLD therapy.
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Affiliation(s)
- Yujie Dong
- The First Affiliated Hospital, Department of Ultrasound Medicine, Hengyang Medical School, University of South China, Hengyang, Hunan421001, China
| | - Minjie Hu
- The First Affiliated Hospital, Department of Cardiothoracic Surgery, Hengyang Medical School, University of South China, Hengyang, Hunan421001, China
| | - Kewei Tan
- The No.922 Hospital of the People Liberation Army Joint Logistics Support Force, Department of the Laboratory and Blood Transfusion, Hengyang, Hunan421002, China
| | - Rongjuan Dai
- The First Affiliated Hospital, Department of Infectious Diseases, Hengyang Medical School, University of South China, Hengyang, Hunan421001, China
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6
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Eun JW, Cheong JY, Jeong JY, Kim HS. A New Understanding of Long Non-Coding RNA in Hepatocellular Carcinoma-From m 6A Modification to Blood Biomarkers. Cells 2023; 12:2272. [PMID: 37759495 PMCID: PMC10528438 DOI: 10.3390/cells12182272] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Revised: 09/12/2023] [Accepted: 09/13/2023] [Indexed: 09/29/2023] Open
Abstract
With recent advancements in biological research, long non-coding RNAs (lncRNAs) with lengths exceeding 200 nucleotides have emerged as pivotal regulators of gene expression and cellular phenotypic modulation. Despite initial skepticism due to their low sequence conservation and expression levels, their significance in various biological processes has become increasingly apparent. We provided an overview of lncRNAs and discussed their defining features and modes of operation. We then explored their crucial function in the hepatocarcinogenesis process, elucidating their complex involvement in hepatocellular carcinoma (HCC). The influential role of lncRNAs within the HCC tumor microenvironment is emphasized, illustrating their potential as key modulators of disease dynamics. We also investigated the significant influence of N6-methyladenosine (m6A) modification on lncRNA function in HCC, enhancing our understanding of both their roles and their upstream regulators. Additionally, the potential of lncRNAs as promising biomarkers was discussed in liver cancer diagnosis, suggesting a novel avenue for future research and clinical application. Finally, our work underscored the dual potential of lncRNAs as both contributors to HCC pathogenesis and innovative tools for its diagnosis. Existing challenges and prospective trajectories in lncRNA research are also discussed, emphasizing their potential in advancing liver cancer research.
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Affiliation(s)
- Jung Woo Eun
- Department of Gastroenterology, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea; (J.W.E.); (J.Y.C.)
| | - Jae Youn Cheong
- Department of Gastroenterology, Ajou University School of Medicine, 164 World cup-ro, Yeongtong-gu, Suwon 16499, Republic of Korea; (J.W.E.); (J.Y.C.)
| | - Jee-Yeong Jeong
- Department of Biochemistry, College of Medicine, Kosin University, Seo-gu, Busan 49267, Republic of Korea;
- Institute for Medical Science, College of Medicine, Kosin University, Seo-gu, Busan 49267, Republic of Korea
| | - Hyung Seok Kim
- Department of Biochemistry, College of Medicine, Kosin University, Seo-gu, Busan 49267, Republic of Korea;
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Zhou Y, Wang Y, Wang Y, Chen L, Wang N, Su Y, Diwu Y, Zhang Q. LncRNA NKILA Exacerbates Alzheimer's Disease Progression by Regulating the FOXA1-Mediated Transcription of TNFAIP1. Neurochem Res 2023:10.1007/s11064-023-03944-6. [PMID: 37217807 DOI: 10.1007/s11064-023-03944-6] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 04/03/2023] [Accepted: 04/20/2023] [Indexed: 05/24/2023]
Abstract
Alzheimer's disease (AD) is one of the most common neurodegenerative diseases in the world, which seriously affects AD patients' life quality. Recently, long non-coding RNAs (lncRNAs) have been reported to play a key role in AD pathogenesis, however, the specific mechanism remains unclear. Herein, we aimed to investigate the role of lncRNA NKILA in AD. The learning and memory performance of rats from streptozotocin (STZ)-treated or other treated groups were tested by Morris water maze test. Relative levels of genes and proteins were measured using RT-qPCR and Western blotting. Mitochondrial membrane potential was tested by JC-1 staining. Levels of ROS, SOD, MDA, GSH-Px, and LDH were measured using corresponding commercial kits. Apoptosis was evaluated by TUNEL staining or Flow cytometry assay. RNA Immunoprecipitation (RIP), RNA pulldown, Chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assays were utilized to test the interaction between indicated molecules. STZ treatment caused learning and memory impairment in rats and oxidative stress damage in SH-SY5Y cells. LncRNA NKILA was found to be elevated in the hippocampal tissues of rats and SH-SY5Y cells after STZ exposure. Knockdown of lncRNA NKILA alleviated STZ-induced neuronal damage. Furthermore, lncRNA NKILA could bind to ELAVL1, which regulate the stability of FOXA1 mRNA. Moreover, TNFAIP1 transcription process was controlled by FOXA1, which targeted the promoter of TNFAIP1. In vivo results demonstrated that lncRNA NKILA accelerated STZ-induced neuronal damage and oxidative stress by FOXA1/TNFAIP1 axis. Our findings indicated that knockdown of lncRNA NKILA inhibited the neuronal damage and oxidative stress induced by STZ through the FOXA1/TNFAIP1 axis, thereby alleviating the development of AD, revealing a promising therapeutic axis for AD treatment.
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Affiliation(s)
- Yuan Zhou
- Department of Anatomy, Basic Medical College, Shaanxi University of Chinese Medicine, Xianyang, 712046, Shaanxi Province, People's Republic of China
- Discipline Innovation Team of Shaanxi, University of Chinese Medicine, Xianyang, 712046, Shaanxi Province, People's Republic of China
- Shaanxi Key Laboratory of Chinese Medicine Encephalopathy, Shaanxi University of Chinese Medicine, Xianyang, 712046, Shaanxi Province, People's Republic of China
- Shaanxi Key Laboratory of Research on TCM Physical Constitution and Diseases Prevention and Treatment, Shaanxi University of Chinese Medicine, Xianyang, 712046, Shaanxi Province, People's Republic of China
| | - Yujin Wang
- Department of TCM Diagnosis, Basic Medical College, Shaanxi University of Chinese Medicine, Xianyang, 712046, Shaanxi Province, People's Republic of China
| | - Yalee Wang
- Discipline Innovation Team of Shaanxi, University of Chinese Medicine, Xianyang, 712046, Shaanxi Province, People's Republic of China
- Affiliated Hospital of Shaanxi University of Chinese Medicine, No.2 Weiyang West Road, Xianyang, 712046, Shaanxi Province, People's Republic of China
| | - Lianji Chen
- Department of Anatomy, Basic Medical College, Shaanxi University of Chinese Medicine, Xianyang, 712046, Shaanxi Province, People's Republic of China
| | - Nan Wang
- Department of Anatomy, Basic Medical College, Shaanxi University of Chinese Medicine, Xianyang, 712046, Shaanxi Province, People's Republic of China
| | - Yanjin Su
- Department of Endocrinology, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, 712046, Shaanxi Province, People's Republic of China.
| | - Yongchang Diwu
- Discipline Innovation Team of Shaanxi, University of Chinese Medicine, Xianyang, 712046, Shaanxi Province, People's Republic of China.
- Basic Medical College, Shaanxi University of Chinese Medicine, Xianyang, 712046, Shaanxi Province, People's Republic of China.
| | - Qi Zhang
- Shaanxi Key Laboratory of Chinese Medicine Encephalopathy, Shaanxi University of Chinese Medicine, Xianyang, 712046, Shaanxi Province, People's Republic of China.
- Shaanxi Key Laboratory of Research on TCM Physical Constitution and Diseases Prevention and Treatment, Shaanxi University of Chinese Medicine, Xianyang, 712046, Shaanxi Province, People's Republic of China.
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8
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Qureshi QUA, Audas TE, Morin RD, Coyle KM. Emerging roles for heterogeneous ribonuclear proteins in normal and malignant B cells. Biochem Cell Biol 2023; 101:160-171. [PMID: 36745874 DOI: 10.1139/bcb-2022-0332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Heterogeneous nuclear ribonucleoproteins (hnRNPs) are among the most abundantly expressed RNA binding proteins in the cell and play major roles in all facets of RNA metabolism. hnRNPs are increasingly appreciated as essential for mammalian B cell development by regulating the carefully ordered expression of specific genes. Due to this tight regulation of the hnRNP-RNA network, it is no surprise that a growing number of genes encoding hnRNPs have been causally associated with the onset or progression of many cancers, including B cell neoplasms. Here we discuss our current understanding of hnRNP-driven regulation in normal, perturbed, and malignant B cells, and the most recent and emerging therapeutic innovations aimed at targeting the hnRNP-RNA network in lymphoma.
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Affiliation(s)
- Qurat Ul Ain Qureshi
- Department of Molecular Biology & Biochemistry, Simon Fraser University, Burnaby, BC, Canada
| | - Timothy E Audas
- Department of Molecular Biology & Biochemistry, Simon Fraser University, Burnaby, BC, Canada
| | - Ryan D Morin
- Department of Molecular Biology & Biochemistry, Simon Fraser University, Burnaby, BC, Canada.,Canada's Michael Smith Genome Sciences Centre at BC Cancer, Vancouver, BC, Canada
| | - Krysta M Coyle
- Department of Molecular Biology & Biochemistry, Simon Fraser University, Burnaby, BC, Canada
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Mukherjee AG, Wanjari UR, Gopalakrishnan AV, Katturajan R, Kannampuzha S, Murali R, Namachivayam A, Ganesan R, Renu K, Dey A, Vellingiri B, Prince SE. Exploring the Regulatory Role of ncRNA in NAFLD: A Particular Focus on PPARs. Cells 2022; 11:3959. [PMID: 36552725 PMCID: PMC9777112 DOI: 10.3390/cells11243959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Revised: 11/29/2022] [Accepted: 12/02/2022] [Indexed: 12/13/2022] Open
Abstract
Liver diseases are responsible for global mortality and morbidity and are a significant cause of death worldwide. Consequently, the advancement of new liver disease targets is of great interest. Non-coding RNA (ncRNA), such as microRNA (miRNA) and long ncRNA (lncRNA), has been proven to play a significant role in the pathogenesis of virtually all acute and chronic liver disorders. Recent studies demonstrated the medical applications of miRNA in various phases of hepatic pathology. PPARs play a major role in regulating many signaling pathways involved in various metabolic disorders. Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver disease in the world, encompassing a spectrum spanning from mild steatosis to severe non-alcoholic steatohepatitis (NASH). PPARs were found to be one of the major regulators in the progression of NAFLD. There is no recognized treatment for NAFLD, even though numerous clinical trials are now underway. NAFLD is a major risk factor for developing hepatocellular carcinoma (HCC), and its frequency increases as obesity and diabetes become more prevalent. Reprogramming anti-diabetic and anti-obesity drugs is an effective therapy option for NAFLD and NASH. Several studies have also focused on the role of ncRNAs in the pathophysiology of NAFLD. The regulatory effects of these ncRNAs make them a primary target for treatments and as early biomarkers. In this study, the main focus will be to understand the regulation of PPARs through ncRNAs and their role in NAFLD.
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Affiliation(s)
- Anirban Goutam Mukherjee
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
| | - Uddesh Ramesh Wanjari
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
| | - Abilash Valsala Gopalakrishnan
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
| | - Ramkumar Katturajan
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
| | - Sandra Kannampuzha
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
| | - Reshma Murali
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
| | - Arunraj Namachivayam
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
| | - Raja Ganesan
- Institute for Liver and Digestive Diseases, Hallym University, Chuncheon 24252, Republic of Korea
| | - Kaviyarasi Renu
- Centre of Molecular Medicine and Diagnostics (COMManD), Department of Biochemistry, Saveetha Dental College & Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai 600077, Tamil Nadu, India
| | - Abhijit Dey
- Department of Life Sciences, Presidency University, Kolkata 700073, West Bengal, India
| | - Balachandar Vellingiri
- Stem Cell and Regenerative Medicine/Translational Research, Department of Zoology, School of Basic Sciences, Central University of Punjab (CUPB), Bathinda 151401, Punjab, India
| | - Sabina Evan Prince
- Department of Biomedical Sciences, School of Biosciences and Technology, Vellore Institute of Technology (VIT), Vellore 632014, Tamil Nadu, India
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10
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Molecular Interactions of the Long Noncoding RNA NEAT1 in Cancer. Cancers (Basel) 2022; 14:cancers14164009. [PMID: 36011001 PMCID: PMC9406559 DOI: 10.3390/cancers14164009] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Revised: 08/16/2022] [Accepted: 08/16/2022] [Indexed: 11/16/2022] Open
Abstract
As one of the best-studied long noncoding RNAs, nuclear paraspeckle assembly transcript 1 (NEAT1) plays a pivotal role in the progression of cancers. NEAT1, especially its isoform NEAT1-1, facilitates the growth and metastasis of various cancers, excluding acute promyelocytic leukemia. NEAT1 can be elevated via transcriptional activation or stability alteration in cancers changing the aggressive phenotype of cancer cells. NEAT1 can also be secreted from other cells and be delivered to cancer cells through exosomes. Hence, elucidating the molecular interaction of NEAT1 may shed light on the future treatment of cancer. Herein, we review the molecular function of NEAT1 in cancer progression, and explain how NEAT1 interacts with RNAs, proteins, and DNA promoter regions to upregulate tumorigenic factors.
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11
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Liu Z, Cao J, Zhang L, Li J, Yan T, Zhou P, Zhang S. Knockdown of circ-PRKCH alleviates IL-1β-treated chondrocyte cell phenotypic changes through modulating miR-502-5p/ADAMTS5 axis. Autoimmunity 2022; 55:179-191. [PMID: 35352613 DOI: 10.1080/08916934.2022.2027918] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/02/2022]
Abstract
BACKGROUND Osteoarthritis (OA) is a common joint disease characterized by progressive cartilage degradation. Circular RNAs (circRNAs) are involved in the initiation and development of OA. This study aimed to explore the potential role and mechanism of circRNA protein kinase C eta (circ-PRKCH) in OA. METHODS A total of 30 cartilage specimens were collected from OA patients or normal subjects. Human chondrocytes (CHON-001) were stimulated with interleukin-1β (IL-1β) to establish an in vitro OA model. The expression levels of circ-PRKCH, microRNA-502-5p (miR-502-5p) and circ-PRKCH or A disintegrin and metalloproteases metallopeptidase with thrombospondin type 1 motif 5 (ADAMTS5) in cartilage specimens and IL-1β-treated chondrocytes were detected by quantitative real-time PCR or Western blot, and their correlation in OA cartilage specimens was analysed by Spearman's correlation coefficient. The targeted relationship between miR-502-5p and circ-PRKCH or ADAMTS5 was verified by dual-luciferase reporter assay and RNA Immunoprecipitation (RIP) assay. Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EDU), flow cytometry, wound healing and enzyme-linked immunosorbent assay (ELISA) assays were applied to evaluate cell proliferation, apoptosis, migration and inflammatory response in IL-1β-treated chondrocytes. Exosomes were identified by transmission electron microscope (TEM) and Western blot. RESULTS Circ-PRKCH and ADAMTS5 expression levels were up-regulated, while miR-502-5p expression was down-regulated in OA cartilage tissues and IL-1β-treated chondrocytes. Depletion of circ-PRKCH relieved IL-1β-treated chondrocyte cell phenotypic changes by promoting cell proliferation and migration, as well as inhibiting apoptosis and inflammatory response. Mechanically, circ-PRKCH acted as a sponge for miR-502-5p to regulate ADAMTS5 expression, thereby contributing to IL-1β-treated chondrocyte cell phenotypic changes. Moreover, exosomes derived from IL-1β-treated chondrocytes could transfer circ-PRKCH across cells. CONCLUSION Circ-PRKCH contributed to IL-1β-treated cell phenotypic changes in chondrocytes via modulating miR-502-5p/ADAMTS5 pathway, which might provide a promising biomarker for OA treatment.
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Affiliation(s)
- Zhongxing Liu
- Department of Orthopedics, Affiliated Hospital of Chifeng University, Institute of Orthopaedic Diseases, Affiliated Hospital of Chifeng University, Chifeng, China
| | - Jian Cao
- Department of Orthopedics, Affiliated Hospital of Chifeng University, Institute of Orthopaedic Diseases, Affiliated Hospital of Chifeng University, Chifeng, China
| | - Limin Zhang
- Department of Orthopedics, Affiliated Hospital of Chifeng University, Institute of Orthopaedic Diseases, Affiliated Hospital of Chifeng University, Chifeng, China
| | - Jinlong Li
- Department of Orthopedics, Affiliated Hospital of Chifeng University, Institute of Orthopaedic Diseases, Affiliated Hospital of Chifeng University, Chifeng, China
| | - Tinghan Yan
- Inner Mongolia University for Nationalities, Chifeng, China
| | - Peng Zhou
- Department of Orthopedics, Affiliated Hospital of Chifeng University, Institute of Orthopaedic Diseases, Affiliated Hospital of Chifeng University, Chifeng, China
| | - Sidi Zhang
- Department of Orthopedics, Affiliated Hospital of Chifeng University, Institute of Orthopaedic Diseases, Affiliated Hospital of Chifeng University, Chifeng, China
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12
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Li D, Fan X, Li Y, Yang J, Lin H. The paradoxical functions of long noncoding RNAs in hepatocellular carcinoma: Implications in therapeutic opportunities and precision medicine. Genes Dis 2022; 9:358-369. [PMID: 35224152 PMCID: PMC8843871 DOI: 10.1016/j.gendis.2020.11.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Revised: 10/22/2020] [Accepted: 11/24/2020] [Indexed: 11/20/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is among the most aggressive and lethal diseases with poor prognosis, worldwide. However, the mechanisms underlying HCC have not been comprehensively elucidated. With the recent application of high-throughput sequencing techniques, a diverse catalogue of differentially expressed long non-coding RNAs (lncRNA) in cancer have been shown to participate in HCC. Rather than being "transcriptional noise," they are emerging as important regulators of many biological processes, including chromatin remodelling, transcription, alternative splicing, translational and post-translational modification. Moreover, lncRNAs have dual effects in the development and progression of HCC, including oncogenic and tumour-suppressive roles. Collectively, recently data point to lncRNAs as novel diagnostic and prognostic biomarkers with satisfactory sensitivity and specificity, as well as being therapeutic targets for HCC patients. In this review, we highlight recent progress of the molecular patterns of lncRNAs and discuss their potential clinical application in human HCC.
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Affiliation(s)
- Duguang Li
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China
- Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China
| | - Xiaoxiao Fan
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China
- Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China
| | - Yirun Li
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China
- Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China
| | - Jing Yang
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China
- Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China
| | - Hui Lin
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China
- Biomedical Research Center, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, PR China
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13
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Lin NC, Hsia SM, Wang TH, Li PJ, Tseng YH, Chiu KC, Tu HF, Shih YH, Shieh TM. The relation between NEAT1 expression level and survival rate in patients with oral squamous cell carcinoma. J Dent Sci 2022; 17:361-367. [PMID: 35028059 PMCID: PMC8739734 DOI: 10.1016/j.jds.2021.09.018] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Revised: 09/08/2021] [Indexed: 02/07/2023] Open
Abstract
Background/purpose Numerous studies have shown that long noncoding RNAs (lncRNAs) are involved in cancer progression and chemotherapy resistance. Nuclear enriched abundant transcript 1 (NEAT1) is an lncRNA. It affects tumor cell progression and drug resistance in various tumors. However, the relation of NEAT1 and survival rate in oral squamous cell carcinoma (OSCC) requires further study. Materials and methods One normal gingival epithelium cell line, SG, three oral cancer cell lines (HSC3, OEC-M1, and SAS), 34 paired non-cancerous matched tissues (NCMT), and OSCC tissues were used in this study. Tri-reagent was used for total RNA extraction. NEAT1 expression was assessed by reverse transcription-quantitative PCR (RT-qPCR). Results NEAT1 expression in oral cancer cell lines was lower than that in normal cells and was significantly downregulated in OSCC. NEAT1 upregulation reduced the survival rate of patients with OSCC. NEAT1 upregulation also reduced the survival rate of OSCC patients treated with chemotherapy and radiotherapy. Conclusion These results indicate that NEAT1 expression is a valuable biomarker for the prediction and prognosis of oral cancer.
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Affiliation(s)
- Nan-Chin Lin
- School of Dentistry, College of Dentistry, China Medical University, Taichung, Taiwan.,Department of Oral and Maxillofacial Surgery, Changhua Christian Hospital, Changhua, Taiwan.,Department of Oral and Maxillofacial Surgery, Show Chwan Memorial Hospital, Changhua, Taiwan
| | - Shih-Min Hsia
- School of Nutrition and Health Sciences, Taipei Medical University, Taipei, Taiwan
| | - Tong-Hong Wang
- Tissue Bank, Chang Gung University, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Po-Jung Li
- School of Dentistry, College of Dentistry, China Medical University, Taichung, Taiwan
| | - Yu-Hsin Tseng
- Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Kuo-Chou Chiu
- Division of Oral Diagnosis and Family Dentistry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Hsi-Feng Tu
- Institute of Oral Biology, School of Dentistry, National Yang-Ming University, Taipei, Taiwan
| | - Yin-Hwa Shih
- Department of Healthcare Administration, College of Medical and Health Science, Asia University, Taichung, Taiwan
| | - Tzong-Ming Shieh
- School of Dentistry, College of Dentistry, China Medical University, Taichung, Taiwan
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14
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Zhang S, Mang Y, Li L, Ran J, Zhao Y, Li L, Gao Y, Li W, Chen G, Ma J. Long noncoding RNA NEAT1 changes exosome secretion and microRNA expression carried by exosomes in hepatocellular carcinoma cells. J Gastrointest Oncol 2021; 12:3033-3049. [PMID: 35070428 PMCID: PMC8748037 DOI: 10.21037/jgo-21-729] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2021] [Accepted: 12/14/2021] [Indexed: 04/06/2024] Open
Abstract
BACKGROUND This study aimed to investigate the roles and functions of nuclear-enriched abundant transcript 1 (NEAT1) in exosome secretion and exosomal microRNA (miRNA) changes in hepatocellular carcinoma (HCC) cells. METHODS HepG2 and HuH-7 cells were divided into two groups: Lv-control (which were infected with lentivirus without NEAT1 expression) and Lv-NEAT1 (which were infected with lentivirus with NEAT1 overexpression). Each group was used to study cell function (proliferation, invasion, and apoptosis) and exosome secretion by nanoparticle tracking analysis (NTA), electron microscopy, and nanoflow cytometry (nanoFCM). Different levels of messenger RNA (mRNA), miRNA, and exosomal miRNA were detected by RNA sequencing. Next, potential target RNAs were verified by reverse transcription polymerase chain reaction (RT-PCR). Changed exosomal miRNAs were found and miRNA mimics were used to study cell function in NEAT1-overexpression and NEAT1-knockdown HCC cells. RESULTS The data showed that NEAT1-overexpression promoted exosome secretion. The overexpression of NEAT1 altered global genes, including exosome-related genes. Compared with the control group, we observed that several miRNAs changed in the exosomes secreted by NEAT1-overexpressing cells. Our study found that these changed exosomal miRNAs played a suppressor role in HCC. Transfection of miR-634, miR-638, and miR-3960 reversed the enhanced invasion and proliferation in HCC cells with a high level of NEAT1 expression. CONCLUSIONS These results suggested that NEAT1 regulates exosome-related genes, which might be associated with increasing exosome secretion by NEAT1-overexpressing cells. Furthermore, NEAT1 promotes cell invasion and proliferation via downregulation of miR-634, miR-638, and miR-3960 in exosomes. This study may provide potential targets for exosome-mediated miRNA transfer in HCCs with a high level of NEAT1 expression therapy.
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Affiliation(s)
- Shengning Zhang
- Department of Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Center, the Calmette Affiliated Hospital of Kunming Medical University, the First People's Hospital of Kunming, Clinical Medical Center for Organ Transplantation of Yunnan Province, Kunming, China
| | - Yuanyi Mang
- Department of Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Center, the Calmette Affiliated Hospital of Kunming Medical University, the First People's Hospital of Kunming, Clinical Medical Center for Organ Transplantation of Yunnan Province, Kunming, China
| | - Li Li
- Department of Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Center, the Calmette Affiliated Hospital of Kunming Medical University, the First People's Hospital of Kunming, Clinical Medical Center for Organ Transplantation of Yunnan Province, Kunming, China
| | - Jianghua Ran
- Department of Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Center, the Calmette Affiliated Hospital of Kunming Medical University, the First People's Hospital of Kunming, Clinical Medical Center for Organ Transplantation of Yunnan Province, Kunming, China
| | - Yingpeng Zhao
- Department of Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Center, the Calmette Affiliated Hospital of Kunming Medical University, the First People's Hospital of Kunming, Clinical Medical Center for Organ Transplantation of Yunnan Province, Kunming, China
| | - Laibang Li
- Department of Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Center, the Calmette Affiliated Hospital of Kunming Medical University, the First People's Hospital of Kunming, Clinical Medical Center for Organ Transplantation of Yunnan Province, Kunming, China
| | - Yang Gao
- Department of Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Center, the Calmette Affiliated Hospital of Kunming Medical University, the First People's Hospital of Kunming, Clinical Medical Center for Organ Transplantation of Yunnan Province, Kunming, China
| | - Wang Li
- Department of Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Center, the Calmette Affiliated Hospital of Kunming Medical University, the First People's Hospital of Kunming, Clinical Medical Center for Organ Transplantation of Yunnan Province, Kunming, China
| | - Guoyu Chen
- Department of Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Center, the Calmette Affiliated Hospital of Kunming Medical University, the First People's Hospital of Kunming, Clinical Medical Center for Organ Transplantation of Yunnan Province, Kunming, China
| | - Jun Ma
- Department of Hepato-Biliary-Pancreatic Surgery and Liver Transplantation Center, the Calmette Affiliated Hospital of Kunming Medical University, the First People's Hospital of Kunming, Clinical Medical Center for Organ Transplantation of Yunnan Province, Kunming, China
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15
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Zhu Y, Xu G, Han C, Xing G. The emerging landscape of long non-coding RNAs in hepatocellular carcinoma. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2021; 14:920-937. [PMID: 34646411 PMCID: PMC8493264] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Accepted: 08/23/2021] [Indexed: 06/13/2023]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common and aggressive cancers. HCC shows high prevalence and lethality caused by a variety of etiologic factors. However, the underlying mechanisms and the diagnostic markers identifying patients at risk in advance has not been entirely elucidated. Long non-coding RNAs (lncRNAs) are a subgroup of non-coding RNAs greater than 200 nucleotides in length with no protein-coding capability. With the progress in sequencing technologies and bioinformatic tools, the landscape of lncRNAs is being revealed. Numerous discoveries point out that lncRNAs participate in HCC carcinogenesis and metastasis through altering cell proliferation and invasion ability, apoptosis, and chemo- or radio-sensitivity. Moreover, lncRNA is easy to detect compared to the traditional diagnostic methods. This review summarizes the mechanisms of major lncRNAs in HCC discovered in recent years and lncRNAs as early diagnostic markers for HCC.
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Affiliation(s)
- Yungang Zhu
- Department of Radiology, Tianjin Teda HospitalTianjin 300457, China
| | - Guoping Xu
- Department of Medical Imaging, The Second Hospital of Tianjin Medical UniversityTianjin 300211, China
| | - Changrui Han
- Department of Radiology, Tianjin Teda HospitalTianjin 300457, China
| | - Gang Xing
- Department of Radiology, Tianjin Teda HospitalTianjin 300457, China
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16
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DiStefano JK, Gerhard GS. Long Noncoding RNAs and Human Liver Disease. ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE 2021; 17:1-21. [PMID: 34416820 DOI: 10.1146/annurev-pathol-042320-115255] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Long noncoding RNAs (lncRNAs) are pervasively transcribed in the genome, exhibit a diverse range of biological functions, and exert effects through a variety of mechanisms. The sheer number of lncRNAs in the human genome has raised important questions about their potential biological significance and roles in human health and disease. Technological and computational advances have enabled functional annotation of a large number of lncRNAs. Though the number of publications related to lncRNAs has escalated in recent years, relatively few have focused on those involved in hepatic physiology and pathology. We provide an overview of evolving lncRNA classification systems and characteristics and highlight important advances in our understanding of the contribution of lncRNAs to liver disease, with a focus on nonalcoholic steatohepatitis, hepatocellular carcinoma, and cholestatic liver disease. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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Affiliation(s)
- Johanna K DiStefano
- Diabetes and Fibrotic Disease Research Unit, Translational Genomics Research Institute, Phoenix, Arizona 85004, USA;
| | - Glenn S Gerhard
- Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania 19140, USA;
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17
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Zhang Y, Chang L, Wu Q, Zuo F. Long non-coding RNA NEAT1 increases the aggressiveness of gastric cancer by regulating the microRNA-142-5p/JAG1 axis. Exp Ther Med 2021; 22:862. [PMID: 34178135 PMCID: PMC8220654 DOI: 10.3892/etm.2021.10294] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2019] [Accepted: 02/25/2021] [Indexed: 02/07/2023] Open
Abstract
Gastric cancer has been indicated to have a high recurrence rate in China. Previous studies have revealed that long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) exerted critical roles in cancers. Therefore, the present study aimed to determine the function of NEAT1 and explore the unknown molecular mechanisms of gastric cancer pathogenesis. Reverse transcription-quantitative PCR assay was used to examine the expression of NEAT1, microRNA (miR)-142-5p and jagged1 (JAG1) in gastric cancer. Cell Counting Kit-8 and Transwell assays were conducted to examine cell proliferation, migration and invasion. The protein expression levels of N-cadherin, Vimentin, E-cadherin and JAG1 were quantified by western blot assay. The associations among NEAT1, miR-142-5p and JAG1 were confirmed by dual-luciferase reporter assay and RNA immunoprecipitation. The effects of NEAT1 silencing on tumor growth were evaluated by tumor xenografts. The results indicated that NEAT1 was highly expressed in tumor tissues and cells compared with that in paracancerous tissues and the normal gastric epithelial cell line GES-1 and significantly associated with poor prognosis in gastric cancer. Functional analyses further demonstrated that NEAT1 knockdown suppressed proliferation, motility and tumor growth in vitro and in vivo. Mechanistically, NEAT1 sponged miR-142-5p to regulate JAG1 expression. In addition, the effects of NEAT1 knockdown on the proliferation, migration and invasion of gastric cancer cells could be rescued by miR-142-5p inhibitor, and JAG1 overexpression reversed the miR-142-5p-mediated effects on gastric cancer cells. These findings demonstrated that long non-coding RNA NEAT1 regulated gastric cancer progression by targeting the miR-142-5p/JAG1 axis.
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Affiliation(s)
- Yanming Zhang
- Department of General Medicine, Yantaishan Hospital, Yantai, Shandong 264001, P.R. China
| | - Liying Chang
- Health Management Center, Qingdao Tumor Hospital, Qingdao, Shandong 266042, P.R. China
| | - Qunmei Wu
- Health Management Center, Qingdao Central Hospital, Qingdao, Shandong 266042, P.R. China
| | - Fang Zuo
- Department of Gastroenterology, Jinan Central Hospital, Jinan, Shandong 250010, P.R. China
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18
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Fan G, Zhang C, Wei X, Wei R, Qi Z, Chen K, Cai X, Xu L, Tang L, Zhou J, Zhang Z, Lin Z, Xie H, Zheng S, Fan W, Xu X. NEAT1/hsa-miR-372-3p axis participates in rapamycin-induced lipid metabolic disorder. Free Radic Biol Med 2021; 167:1-11. [PMID: 33705959 DOI: 10.1016/j.freeradbiomed.2021.02.033] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 02/20/2021] [Accepted: 02/24/2021] [Indexed: 12/11/2022]
Abstract
Rapamycin is a crucial immunosuppressive regimen for patients that have undergone liver transplantation (LT). However, one of the major side effects of rapamycin include metabolic disorders such as dyslipidemia, and the mechanism remains unknown. This study aims to explore the biomolecules that are responsible for rapamycin-induced dyslipidemia and the control strategies that can reverse the lipid metabolism disorder. In this study, data collected from LT patients, cell and mouse models treated with rapamycin were analyzed. Results showed an increase of triglycerides (TGs) induced by rapamycin. MicroRNAs (miRNAs) play important roles in many vital biological processes including TG metabolism. hsa-miR-372-3p was filtered using RNA sequencing and identified as a key regulator in rapamycin-induced TGs accumulation. Using bioinformatics and experimental analyses, target genes of hsa-miR-372-3p were predicted. These genes were alkylglycerone phosphate synthase (AGPS) and apolipoprotein C4 (APOC4), which are reported to be involved in TG metabolism. LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) was also identified as an upstream regulatory factor of hsa-miR-372-3p. From the results of this study, NEAT1/hsa-miR-372-3p/AGPS/APOC4 axis plays a vital role in rapamycin-disruption of lipid homeostasis. Therefore, targeting this axis is a potential therapeutic target combating rapamycin-induced dyslipidemia after LT.
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Affiliation(s)
- Guanghan Fan
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Chenzhi Zhang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Xuyong Wei
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Rongli Wei
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Zhetuo Qi
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Kangchen Chen
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Xuechun Cai
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Li Xu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Linsong Tang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Junbin Zhou
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Zhensheng Zhang
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Zuyuan Lin
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Haiyang Xie
- NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China
| | - Shusen Zheng
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China; Department of Hepatobiliary and Pancreatic Surgery, Shulan (Hangzhou) Hospital, Hangzhou, 310000, China
| | - Weimin Fan
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China; Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, 29425, USA
| | - Xiao Xu
- Department of Hepatobiliary and Pancreatic Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, 310006, China; Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, 79 Qingchun Road, Hangzhou, 310003, China; NHC Key Laboratory of Combined Multi-organ Transplantation, Hangzhou, 310003, China.
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lncRNA HEIH accelerates cell proliferation and inhibits cell senescence by targeting miR-3619-5p/CTTNBP2 axis in ovarian cancer. ACTA ACUST UNITED AC 2021; 27:1302-1314. [PMID: 33110047 DOI: 10.1097/gme.0000000000001655] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVE Epithelial ovarian cancer is the most lethal malignancy in gynecology. Numerous studies have confirmed that long noncoding RNAs (lncRNAs) are abnormally expressed in ovarian cancer and are closely associated with the cell proliferation and senescence in cancers. However, the role and underlying molecular mechanism of long noncoding RNA high expression in hepatocellular carcinoma (HEIH) in ovarian cancer remain unknown. METHODS Experiments including Real-time quantitative polymerase chain reaction, RNA immunoprecipitation, luciferase reporter, Fluorescence in situ hybridization, western blot, colony formation assays, β-galactosidase senescence assay, cell apoptosis, proliferation, invasion, and migration assays were applied to investigate the role of HEIH in ovarian cancer. The data were expressed as the mean ± standard deviation. Student t test was used to compare the data between two groups. The one-way analysis of variance was applied to compare the data among multiple groups with Tukey post hoc test. All experiments were repeated three times. P < 0.05 was considered statistically significant. RESULTS Herein, HEIH expression was found to be up-regulated in ovarian cancer tissues (n = 25; twofold higher than normal tissues, P < 0.05) and cell lines (sixfold higher than normal ovarian epithelial cell line on average, P < 0.05), and high HEIH expression predicted poor prognosis (survival rate is about 25% after 40 mo; P < 0.05). Moreover, we found that HEIH accelerated proliferation, migration, and invasion, whereas inhibited cell senescence in ovarian cancer (P < 0.05). In mechanism, HEIH was confirmed to serve as a sponge for miR-3619-5p, and miR-3619-5p counteracted HEIH-mediated regulation of ovarian cancer (P < 0.05). Besides, cortactin-binding protein 2 (CTTNBP2) was found to be the downstream target of miR-3619-5p. Rescue assays validated that CTTNBP2 up-regulation significantly reversed the inhibitory effects of HEIH knockdown on ovarian cancer progression (P < 0.05). Furthermore, we found that HEIH facilitated tumor growth in vivo by regulating CTTNBP2 expression (P < 0.05). CONCLUSIONS In conclusion, our research revealed that HEIH accelerated cell proliferation, migration and invasion, whereas inhibited cell senescence in ovarian cancer via targeting the miR-3619-5p/CTTNBP2 axis. These findings may be valuable for finding new therapeutic targets to improve ovarian cancer treatment.
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Wang Z, Gu J, Yan A, Li K. Downregulation of circ-RANBP9 in laryngeal cancer and its clinical significance. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:484. [PMID: 33850881 PMCID: PMC8039645 DOI: 10.21037/atm-21-567] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Background Laryngeal cancer (LC) is a common malignant tumor of the head and neck. As circular RNAs (circRNAs) and other non-coding RNAs are involved in various malignant processes, we analyzed circRNAs to better understand LC and explored specific tumor markers. Methods High-throughput sequence was performed to analyze the differential circular RNAs in four coupled laryngeal cancers and para-cancerous tissues. The differential expression of selected circ-RANBP9 in laryngeal cancer tissues and cells was verified by RT-qPCR assay. CCK8, EDU, Transwell and wound healing assays were used to confirm the biological function of circ-RANBP9 in laryngeal cancer. Western blot assay was performed to identify the effects of circ-RANBP9 having on the epithelial to mesenchymal transition process. One-way AN0VA was used to analyze the correlation between the expression of circ-RANBP9 and clinicopathological parameters of the included patients. Kaplan-Meier analysis was used to investigate whether the expression level of circ-RANBP9 correlated with survival in LC patients. Bioinformatic analyses were also conducted to predict the functions and possible signaling pathways of the targeted mRNAs of circ-RANBP9 via co-expression and competing endogenous RNA network. Results We found a transcript from RNA sequence data, termed hsa_circ_0001578, which is a circRNA spliced from RANBP9. Circ-RANBP9 was downregulated in the LC cell lines tissues, relating to a better prognosis. Circ-RANBP9 was found to inhibit the proliferation, migration, and invasion ability of LC, exerting a suppressive role in the epithelial to mesenchymal transition process as well. For the diagnostic value of circ-RANBP9, the sensitivity and the specificity were 0.979 and 0.553, respectively. Circ-RANBP9 downregulation was significantly correlated with differentiation (P=0.031), T-stage (P=0.018), lymphatic metastasis (P=0.046), and clinical stage (P=0.003). Circ-RANBP9 was involved in insulin-like growth factor receptor binding, cell polarity, focal adhesion, and MAPK signaling pathways. CeRNA analysis identified the possible involvement of circ-RANBP9 in the ECM-receptor interaction, cAMP, calcium, and Wnt signaling pathways by harboring miRNA genes. Conclusions Circ-RANBP9 was confirmed to play important roles in inhibiting laryngeal cancers. Circ-RANBP9 was also validated to be associated with the clinicopathological parameters and diagnostic value, suggesting that circ-RANBP9 is a promising biomarker for LC prognosis and early diagnosis.
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Affiliation(s)
- Zheng Wang
- Department of Otorhinolaryngology, the First Affiliated Hospital of China Medical University, Shenyang, China
| | - Jia Gu
- Department of Otorhinolaryngology, the First Affiliated Hospital of China Medical University, Shenyang, China
| | - Aihui Yan
- Department of Otorhinolaryngology, the First Affiliated Hospital of China Medical University, Shenyang, China
| | - Kai Li
- Department of Surgical Oncology, the First Affiliated Hospital of China Medical University, Shenyang, China
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21
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Lei R, Feng L, Hong D. ELFN1-AS1 accelerates the proliferation and migration of colorectal cancer via regulation of miR-4644/TRIM44 axis. Cancer Biomark 2020; 27:433-443. [PMID: 31929141 DOI: 10.3233/cbm-190559] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Faced with the increasing colorectal cancer (CRC) cases, the interrogation of pivotal molecules in CRC appears to be vitally important. Long non-coding RNAs (lncRNAs) are well-known regulators of gene expression at transcriptional, post-transcriptional or epigenetic level, among which the competing endogenous RNA (ceRNA) network is a common way that lncRNAs exert their properties. The current study aimed to provide a new insight into improving the outcomes of CRC patients. Our study detected that ELFN1-AS1 expression was elevated in CRC tissues and cells, and ELFN1-AS1 upregulation was correlated with poor prognosis of CRC sufferers. Besides, it was viewed that ELFN1-AS1 knockdown impeded the proliferation and migration abilities as well as activated the apoptosis ability of CRC cells. In subsequence, mechanism assays also displayed that ELFN1-AS1 targeted miR-4644 to augment TRIM44 level. Finally, rescue experiments confirmed that TRIM44 took part in the ELFN1-AS1-medatied promotional influences on CRC cells proliferation and migration. In conclusion, ELFN1-AS1 exerted pro-proliferation, anti-apoptosis and pro-migration functions on CRC cells by acting as a sponge of miR-4644 to increase TRIM44 expression at mRNA and protein level, providing an additional molecule responsible for the carcinogenesis and progression for CRC.
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Affiliation(s)
- Ren Lei
- Gastrointestinal Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Liuchun Feng
- Respiratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
| | - Deng Hong
- Gastrointestinal Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China
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Bu FT, Wang A, Zhu Y, You HM, Zhang YF, Meng XM, Huang C, Li J. LncRNA NEAT1: Shedding light on mechanisms and opportunities in liver diseases. Liver Int 2020; 40:2612-2626. [PMID: 32745314 DOI: 10.1111/liv.14629] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Revised: 07/10/2020] [Accepted: 07/26/2020] [Indexed: 12/24/2022]
Abstract
With advances in genome and transcriptome research technology, the function and mechanism of lncRNAs in physiological and pathological states have been gradually revealed. Nuclear Enriched Abundant Transcript 1 (NEAT1, a long non-coding RNA), a vital component of paraspeckles, plays an indispensable role in the formation and integrity of paraspeckles. Throughout the research history, NEAT1 is mostly aberrantly upregulated in various cancers, and high expression of NEAT1 often contributes to poor prognosis of patients. Notably, the role and mechanism of NEAT1 in liver diseases have been increasingly reported. NEAT1 accelerates the progression of non-alcoholic fatty liver disease (NAFLD), liver fibrosis and hepatocellular carcinoma, while exerting a protective role in the pathogenesis of acute-on-chronic liver failure by inhibiting the inflammatory response. In this review, we will elaborate on relevant studies on the different casting of NEAT1 in liver diseases, especially focusing on its regulatory mechanisms and new opportunities for alcoholic liver disease.
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Affiliation(s)
- Fang-Tian Bu
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.,The Key Laboratory of Anti-Inflammatory of Immune Medicines, Ministry of Education, Hefei, China.,Institute for Liver Diseases of Anhui Medical University, Hefei, China
| | - Ao Wang
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.,The Key Laboratory of Anti-Inflammatory of Immune Medicines, Ministry of Education, Hefei, China.,Institute for Liver Diseases of Anhui Medical University, Hefei, China
| | - Yan Zhu
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.,The Key Laboratory of Anti-Inflammatory of Immune Medicines, Ministry of Education, Hefei, China.,Institute for Liver Diseases of Anhui Medical University, Hefei, China
| | - Hong-Mei You
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.,The Key Laboratory of Anti-Inflammatory of Immune Medicines, Ministry of Education, Hefei, China.,Institute for Liver Diseases of Anhui Medical University, Hefei, China
| | - Ya-Fei Zhang
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.,The Key Laboratory of Anti-Inflammatory of Immune Medicines, Ministry of Education, Hefei, China.,Institute for Liver Diseases of Anhui Medical University, Hefei, China
| | - Xiao-Ming Meng
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.,The Key Laboratory of Anti-Inflammatory of Immune Medicines, Ministry of Education, Hefei, China.,Institute for Liver Diseases of Anhui Medical University, Hefei, China
| | - Cheng Huang
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.,The Key Laboratory of Anti-Inflammatory of Immune Medicines, Ministry of Education, Hefei, China.,Institute for Liver Diseases of Anhui Medical University, Hefei, China
| | - Jun Li
- Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei, China.,The Key Laboratory of Anti-Inflammatory of Immune Medicines, Ministry of Education, Hefei, China.,Institute for Liver Diseases of Anhui Medical University, Hefei, China
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Khalifa O, Errafii K, Al-Akl NS, Arredouani A. Noncoding RNAs in Nonalcoholic Fatty Liver Disease: Potential Diagnosis and Prognosis Biomarkers. DISEASE MARKERS 2020; 2020:8822859. [PMID: 33133304 PMCID: PMC7593715 DOI: 10.1155/2020/8822859] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 07/25/2020] [Accepted: 07/31/2020] [Indexed: 12/14/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide in part due to the concomitant obesity pandemic and insulin resistance (IR). It is increasingly becoming evident that NAFLD is a disease affecting numerous extrahepatic vital organs and regulatory pathways. The molecular mechanisms underlying the nonalcoholic steatosis formation are poorly understood, and little information is available on the pathways that are responsible for the progressive hepatocellular damage that follows lipid accumulation. Recently, much research has focused on the identification of the epigenetic modifications that contribute to NAFLD pathogenesis. Noncoding RNAs (ncRNAs) are one of such epigenetic factors that could be implicated in the NAFLD development and progression. In this review, we summarize the current knowledge of the genetic and epigenetic factors potentially underlying the disease. Particular emphasis will be put on the contribution of microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs) to the pathophysiology of NAFLD as well as their potential use as therapeutic targets or as markers for the prediction and the progression of the disease.
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Affiliation(s)
- Olfa Khalifa
- Diabetes Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar
| | - Khaoula Errafii
- Diabetes Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar
- College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Education City, Doha, Qatar
| | - Nayla S. Al-Akl
- Diabetes Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar
| | - Abdelilah Arredouani
- Diabetes Research Center, Qatar Biomedical Research Institute, Hamad Bin Khalifa University, Qatar Foundation, Doha, Qatar
- College of Health and Life Sciences, Hamad Bin Khalifa University, Qatar Foundation, Education City, Doha, Qatar
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Zhang X, Kang Z, Xie X, Qiao W, Zhang L, Gong Z, Chen Y, Shen W. Silencing of HIF-1α inhibited the expression of lncRNA NEAT1 to suppress development of hepatocellular carcinoma under hypoxia. Am J Transl Res 2020; 12:3871-3883. [PMID: 32774741 PMCID: PMC7407699] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Accepted: 06/02/2020] [Indexed: 06/11/2023]
Abstract
BACKGROUND We aimed to explore the relationship between hypoxia-inducible factors-1α (HIF-1α) and lncRNA nuclear-enriched abundant transcript 1 (NEAT1), and their functions on hepatocellular carcinoma (HCC) under hypoxia. METHODS HIF-1α and NEAT1 levels in HCC tissues and corresponding non-tumor tissues were determined by qRT-PCR, and the correlations of their levels in HCC tissues were analyzed by Pearson test. The relationship between overall survival and the two genes (HIF-1α and NEAT1) for HCC patients was detected by log-rank test. Clinicopathological features of NEAT1 in HCC patients were collected. HIF-1α and NEAT1 levels in HCC cells were measured by qRT-PCR and Western blot, and their relationship was determined by co-immunoprecipitation (Co-IP) assay. Cell viability, migration and invasion were detected by CCK-8, scratch wound healing and transwell assay, respectively. The interaction of NEAT1 with HIF-1α in tumor development was determined by xenograft tumor assays in nude mice. RESULTS NEAT1 and HIF-1α were highly expressed and showed a positive relationship in HCC tissues, and specifically, higher NEAT1 expression was positively associated with advanced TNM stage and metastasis in HCC patients. Up-regulated NEAT1 or HIF-1α in HCC patients had poorer prognosis. NEAT1 was induced by HIF-1α and suppressed by siHIF-1α. NEAT1 overexpression further promoted development of HCC under hypoxia while promoting cell viability, migration and invasion and suppressing apoptosis, and such effects were reversed by down-regulating HIF-1α. NEAT1 overexpression promoted tumor growth, which was reversed by down-regulating HIF-1α. CONCLUSION HIF-1α knockdown inhibits NEAT1 expression, which suppresses progression of HCC and improves its prognosis.
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Affiliation(s)
- Xiuming Zhang
- Department of Radiology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical UniversityNanjing, China
| | - Zheng Kang
- Department of Radiology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical UniversityNanjing, China
| | - Xiaodong Xie
- Department of Radiology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical UniversityNanjing, China
| | - Wei Qiao
- Department of Radiology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical UniversityNanjing, China
| | - Lei Zhang
- Department of Radiology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical UniversityNanjing, China
| | - Zhen Gong
- Department of Gynecology, Women’s Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care HospitalNanjing, China
| | - Yan Chen
- Department of Radiology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical UniversityNanjing, China
| | - Wenrong Shen
- Department of Radiology, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical UniversityNanjing, China
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Qin H, Ni H, Liu Y, Yuan Y, Xi T, Li X, Zheng L. RNA-binding proteins in tumor progression. J Hematol Oncol 2020; 13:90. [PMID: 32653017 PMCID: PMC7353687 DOI: 10.1186/s13045-020-00927-w] [Citation(s) in RCA: 228] [Impact Index Per Article: 45.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Accepted: 06/25/2020] [Indexed: 02/08/2023] Open
Abstract
RNA-binding protein (RBP) has a highly dynamic spatiotemporal regulation process and important biological functions. They are critical to maintain the transcriptome through post-transcriptionally controlling the processing and transportation of RNA, including regulating RNA splicing, polyadenylation, mRNA stability, mRNA localization, and translation. Alteration of each process will affect the RNA life cycle, produce abnormal protein phenotypes, and thus lead to the occurrence and development of tumors. Here, we summarize RBPs involved in tumor progression and the underlying molecular mechanisms whereby they are regulated and exert their effects. This analysis is an important step towards the comprehensive characterization of post-transcriptional gene regulation involved in tumor progression.
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Affiliation(s)
- Hai Qin
- School of Life Science and Technology, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, People's Republic of China
| | - Haiwei Ni
- School of Life Science and Technology, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, People's Republic of China
| | - Yichen Liu
- School of Life Science and Technology, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, People's Republic of China
| | - Yaqin Yuan
- Guizhou Medical Device Testing Center, Guiyang, 550004, Guizhou, People's Republic of China
| | - Tao Xi
- School of Life Science and Technology, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, People's Republic of China.
| | - Xiaoman Li
- Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, People's Republic of China.
| | - Lufeng Zheng
- School of Life Science and Technology, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 639 Longmian Road, Nanjing, 211198, People's Republic of China.
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De Vincentis A, Rahmani Z, Muley M, Vespasiani-Gentilucci U, Ruggiero S, Zamani P, Jamialahmadi T, Sahebkar A. Long noncoding RNAs in nonalcoholic fatty liver disease and liver fibrosis: state-of-the-art and perspectives in diagnosis and treatment. Drug Discov Today 2020; 25:1277-1286. [PMID: 32439605 DOI: 10.1016/j.drudis.2020.05.009] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 04/03/2020] [Accepted: 05/11/2020] [Indexed: 02/07/2023]
Abstract
Nonalcoholic fatty liver disease (NAFLD) significantly impacts global health. Despite considerable research, its pathophysiology remains partially unclear. In addition, selective serum biomarkers of disease diagnosis and progression are missing. Long noncoding RNAs (lncRNAs) are a heterogeneous group of ncRNAs with crucial roles in biological processes underlying the pathophysiology of different human diseases. Recent studies have shown that lncRNA could be associated with the genesis and progression of NAFLD towards the most severe forms. Although the field is still in its infancy, it is tempting to speculate that these transcripts could be used as both diagnostic and therapeutic targets. In this review, we summarize recent findings on lncRNAs in the complex research field of NAFLD.
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Affiliation(s)
- Antonio De Vincentis
- Clinical Medicine and Hepatology Unit, Campus Bio-Medico University of Rome, via Alvaro del Portillo, 200, 00128 Rome, Italy
| | - Zahra Rahmani
- Department of Medical Genetics, Golestan University of Medical Sciences, Gorgan, Iran
| | - Moises Muley
- Clinical Medicine and Hepatology Unit, Campus Bio-Medico University of Rome, via Alvaro del Portillo, 200, 00128 Rome, Italy
| | - Umberto Vespasiani-Gentilucci
- Clinical Medicine and Hepatology Unit, Campus Bio-Medico University of Rome, via Alvaro del Portillo, 200, 00128 Rome, Italy
| | - Sergio Ruggiero
- Clinical Medicine and Hepatology Unit, Campus Bio-Medico University of Rome, via Alvaro del Portillo, 200, 00128 Rome, Italy
| | - Parvin Zamani
- Student Research Committee, Department of Medical Biotechnology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Tannaz Jamialahmadi
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Amirhossein Sahebkar
- Halal Research Center of IRI, FDA, Tehran, Iran; Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad 9177948564, Iran; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
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Niu Y, Tang G, Wu X, Wu C. LncRNA NEAT1 modulates sorafenib resistance in hepatocellular carcinoma through regulating the miR-149-5p/AKT1 axis. Saudi J Gastroenterol 2020; 26:285018. [PMID: 32461380 PMCID: PMC7580733 DOI: 10.4103/sjg.sjg_4_20] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/06/2020] [Revised: 03/31/2020] [Accepted: 04/11/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND/AIMS The purpose of this study is to explore the expression characteristics of lncRNA NEAT1 in hepatocellular carcinoma (HCC) and the molecular mechanism of its regulation on sorafenib resistance. MATERIALS AND METHODS This experimental study was performed from June 2013 to June 2019. The level of NEAT1 was determined using RT-PCR in HCC and matched adjacent tissues from 79 HCC patients in Linyi central hospital. The patients were divided into two groups to compare their prognosis based on the median NEAT1 expressions as a cutoff value. HCC cell line HepG2 negative control (HepG2-NC), sorafenib-resistant HepG2 cells (HepG2-SR) were transfected with or without NEAT1 siRNA, followed by subsequent molecular analysis, to determine the function of NEAT1 on sorafenib resistance in HCC cells. The cell transcripts were determined by RNA-sequencing analysis. The binding site of the NEAT1 and microRNA-149-5p (miR-149-5p) was verified by luciferase assay. RESULTS We found that NEAT1 was significantly increased in HCC tissues. Furthermore, NEAT1 expressions were significantly associated with HCC prognosis and chemoresistance patterns against sorafenib. Subsequently, the sorafenib-resistant HCC cell lines, together with the controls, were used to determine the regulatory effect of NEAT1 on HCC cells' progression and sorafenib resistance. NEAT1 targets the miR-149-5p, and therefore, decrease the activity of sorafenib against HCC cells. NEAT1 functions were demonstrated to be triggered by the regulation of miR-149-5p/AKT1 axis. CONCLUSIONS NEAT1/miR-149-5p/AKT1 pathway-based therapy might be a potential clinical application for HCC patients.
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Affiliation(s)
- Yuexiang Niu
- Department of Infectious Diseases, Linyi Central Hospital, Linyi, Shandong, P.R. China
| | - Gongen Tang
- Department of Infectious Diseases, Linyi Central Hospital, Linyi, Shandong, P.R. China
| | - Xiuli Wu
- Department of Respiration, Yishui people's Hospital, Linyi, Shandong, P.R. China
| | - Chaoyu Wu
- Department of Infectious Diseases, Linyi Central Hospital, Linyi, Shandong, P.R. China
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Kim YA, Park KK, Lee SJ. LncRNAs Act as a Link between Chronic Liver Disease and Hepatocellular Carcinoma. Int J Mol Sci 2020; 21:2883. [PMID: 32326098 PMCID: PMC7216144 DOI: 10.3390/ijms21082883] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2020] [Revised: 04/16/2020] [Accepted: 04/18/2020] [Indexed: 12/13/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) are emerging as important contributors to the biological processes underlying the pathophysiology of various human diseases, including hepatocellular carcinoma (HCC). However, the involvement of these molecules in chronic liver diseases, such as nonalcoholic fatty liver disease (NAFLD) and viral hepatitis, has only recently been considered in scientific research. While extensive studies on the pathogenesis of the development of HCC from hepatic fibrosis have been conducted, their regulatory molecular mechanisms are still only partially understood. The underlying mechanisms related to lncRNAs leading to HCC from chronic liver diseases and cirrhosis have not yet been entirely elucidated. Therefore, elucidating the functional roles of lncRNAs in chronic liver disease and HCC can contribute to a better understanding of the molecular mechanisms, and may help in developing novel diagnostic biomarkers and therapeutic targets for HCC, as well as in preventing the progression of chronic liver disease to HCC. Here, we comprehensively review and briefly summarize some lncRNAs that participate in both hepatic fibrosis and HCC.
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Affiliation(s)
| | | | - Sun-Jae Lee
- Department of Pathology, Catholic University of Daegu School of Medicine, Daegu 42472, Korea; (Y.-A.K.); (K.-K.P.)
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Zhang L, Chen Y, Bao C, Zhang X, Li H. Eukaryotic initiation Factor 4AIII facilitates hepatocellular carcinoma cell proliferation, migration, and epithelial-mesenchymal transition process via antagonistically binding to WD repeat domain 66 with miRNA-2113. J Cell Physiol 2020; 235:8199-8209. [PMID: 31975383 DOI: 10.1002/jcp.29475] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Accepted: 01/08/2020] [Indexed: 12/22/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the malignant cancers with high incidence and mortality rates worldwide. RNA-binding protein eukaryotic initiation Factor 4A-III (eIF4AIII) is a carcinogene in the biological process of tumors and microRNA (miRNA)-2113 has rarely been studied in cancers, not to mention in HCC. The regulation mechanism between eIF4AIII and miR-2113 involved in HCC is yet to be explored. The purpose of this research is to probe the function role and associated underlying mechanism of eIF4AIII participated in HCC. The results revealed that eIF4AIII was overexpressed in HCC. Lost-of-function assays found that eIF4AIII knockdown, WD (Trp-Asp [tryptophan and asparaginic acid]) repeat domain 66 (WDR66) silence or miR-2113 promotion repressed cell proliferation, migration, and epithelial-mesenchymal transition (EMT) process in HCC. Furthermore, eIF4AIII could interact with WDR66 and further stabilize WDR66 messenger RNA. In addition, WDR66 was a target gene of miR-2113. Besides, WDR66 was antagonistically regulated by eIF4AIII and miR-2113. Rescue assays verified that eIF4AIII promoted HCC cell proliferation, migration, and EMT process via antagonistically binding to WDR66 with miR-2113. Taken together, these findings indicated an important role and a novel mechanism of eIF4AIII in HCC, providing an optional therapy for HCC patients.
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Affiliation(s)
- Li Zhang
- Department of Radiation and Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yangzong Chen
- Division of PET/CT, Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Chunchun Bao
- Division of PET/CT, Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xiuxing Zhang
- Division of PET/CT, Department of Radiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Haiying Li
- Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
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Chen R, Zhang X, Wang C. LncRNA HOXB-AS1 promotes cell growth in multiple myeloma via FUT4 mRNA stability by ELAVL1. J Cell Biochem 2019; 121:4043-4051. [PMID: 31886581 DOI: 10.1002/jcb.29573] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Accepted: 12/09/2019] [Indexed: 12/11/2022]
Abstract
Multiple myeloma (MM) is defined as the second most common hematological tumor in the globe. Long noncoding RNAs (lncRNAs) have been reported to play stimulative or suppressive role in the progression of different carcinomas. The investigation of lncRNAs in MM is still inadequate. LncRNA HOXB cluster antisense RNA 1 (HOXB-AS1) was once revealed to facilitate glioma progression by affecting cellular activities of glioma cells. However, whether HOXB-AS1 participates in the development of MM still remains an enigma. In this study, we unveiled that HOXB-AS1 was highly expressed in MM and loss-of-function assays certified that HOXB-AS1 obstruction suppressed MM cell proliferation, and stimulated cell apoptosis. In addition, HOXB-AS1 could modulate fucosyltransferase 4 (FUT4) and FUT4-mediated Wnt/β-catenin pathway. In subsequence, it was observed from mechanism assays that HOXB-AS1 enhanced the interaction between ELAVL1 and FUT4 so as to stabilize FUT4 messenger RNA. In the end, rescue experiments affirmed that HOXB-AS1 affected the cell growth through FUT4 in MM. In conclusion, the whole modulation mechanism of HOXB-AS1/ELAVL1/FUT4 axis in MM was validated in this study, which suggested that HOXB-AS1 might function as a powerful and promising therapeutic biomarker for the clinical treatment of patients with MM.
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Affiliation(s)
- Rongsheng Chen
- Department of Spinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Xiaobo Zhang
- Department of Spinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
| | - Changsheng Wang
- Department of Spinal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China
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BCLAF1 promotes cell proliferation, invasion and drug-resistance though targeting lncRNA NEAT1 in hepatocellular carcinoma. Life Sci 2019; 242:117177. [PMID: 31870774 DOI: 10.1016/j.lfs.2019.117177] [Citation(s) in RCA: 38] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2019] [Revised: 12/11/2019] [Accepted: 12/12/2019] [Indexed: 01/11/2023]
Abstract
AIMS In the present research, we aimed to investigate the effect of Bcl-2-associated transcription factor 1 (BCLAF1) on hepatocellular carcinoma and further explore the special molecular mechanism. MAIN METHODS The expression of BCLAF1 was analyzed in tumor tissues and different hepatocellular cancer cell lines by real-time RT-PCR and Western blot. Cell proliferation and invasion was explored using MTT and Transwell assay respectively. In addition, luciferase reporter assay was performed to determine the binding activity of BCLAF1 and Nuclear enrichment-rich transcription factor 1 (NEAT1) promoter. Finally, the IC50 for 5-Fluorouracil (5-Fu) was measured by MTT assay, and Western blot was used to determine the expression of P-glycoprotein (P-gp) and multidrug resistance protein1 (MRP1). KEY FINDING The result revealed that BCLAF1 was highly expressed in hepatocellular carcinoma tissues and cells. In addition, BCLAF1-siRNA inhibited the proliferation and invasion of hepatocellular carcinoma cells, and overexpression of BCLAF1 promoted proliferation and invasion. Furthermore, luciferase reporter assay demonstrated that BCLAF1 directly interact with lncNEAT1 promoter and improved NEAT1 expression, and BCLAF1 promoted proliferation and invasion through targeting lncRNA NEAT1. What's more, BCLAF1 promoted 5-Fu resistance and the expression of P-gp and MRP1 in hepatocellular carcinoma cells by targeting NEAT1. SIGNIFICANCE The results of the present study suggested that BCLAF1 might be a new gene related to proliferation and drug-resistance of hepatocellular carcinoma. In the future, the search for a deep and reasonable mechanism for the role of BCLAF1 will help us to understand its function more comprehensively, and finally find a new method for the treatment of human cancer.
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Liu Q, Shi H, Yang J, Jiang N. Long Non-Coding RNA NEAT1 Promoted Hepatocellular Carcinoma Cell Proliferation and Reduced Apoptosis Through the Regulation of Let-7b-IGF-1R Axis. Onco Targets Ther 2019; 12:10401-10413. [PMID: 31819522 PMCID: PMC6890520 DOI: 10.2147/ott.s217763] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Accepted: 10/15/2019] [Indexed: 12/28/2022] Open
Abstract
Background and aim Long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) is abnormally expressed in various human malignancies, including hepatocellular carcinoma (HCC). Let-7b is a miRNA with the effect of a tumor suppressor gene, and its expression level in various tumor tissues is lower than that in normal tissues. Studies have found that IGF-1R can be abnormally activated in the process of hepatocyte deterioration, and the expression level of IGF-1R in HCC is significantly up-regulated. The aim of this study was to investigate the functional mechanism of NEAT1/let-7b-IGF-1R axis in HCC. Methods The expressions of NEAT1 and microRNA (miR)-let-7b in HCC tissues and cell lines were quantified by quantitative real-time PCR (qRT-PCR). The effect of NEAT1 on tumor growth was observed in a mice model of transplanted hepatoma. The effects of down-regulation or up-regulation of NEAT1 expression in HCC cell lines were analysed from the perspectives of cell viability and apoptosis. The binding sites of NEAT1 and miR-let-7b were predicted by biological software. The expression of the miR-let-7b target molecules IGF-1R was detected by Western blotting. Results The results showed that the expressions of NEAT1 were significantly increased, while the expressions of miR-let-7b were decreased in the HCC tissues and cell lines. Additionally, it was found that the expressions of NEAT1 and miR-let-7b showed a negative correlation in HCC tissues. The mouse model experiments confirmed that the interference with NEAT1 expression inhibited the tumor growth. Meanwhile, the cell viability of HepG2/Huh7 cell lines was significantly decreased via the downregulation of NEAT1, whereas the corresponding rates of apoptosis were significantly increased. It was further proven that there was a certain negative regulatory mechanism between NEAT1 and miR-1et-7b, which was related to the expression of IGF-1R. Conclusion The over-expression of NEAT1 could promote the proliferation of HCC cells by inhibiting the expression of the miR-let-7b regulated by IGF-1R.
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Affiliation(s)
- Qin Liu
- Department of Gastroenterology, Weihai Municipal Hospital, Weihai, People's Republic of China
| | - Hexian Shi
- Department of Hepatobiliary Surgery, Heze Municipal Hospital, Heze, People's Republic of China
| | - Jianbo Yang
- Department of Oral Medicine, Weihai Stomatological Hospital, Weihai, People's Republic of China
| | - Ning Jiang
- Department of General Surgery, Shandong Provincial Third Hospital, Jinan, People's Republic of China
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Wu Q, Ma J, Meng W, Hui P. DLX6-AS1 promotes cell proliferation, migration and EMT of gastric cancer through FUS-regulated MAP4K1. Cancer Biol Ther 2019; 21:17-25. [PMID: 31591939 DOI: 10.1080/15384047.2019.1647050] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Gastric cancer (GC) is the second most prevalent carcinoma resulting in cancer-related deaths in the world, with differences among geographic areas. Although the incidence and mortality rates of GC in Asia are decreasing, the search for diverse and effective therapies of GC is still needed to be fully inquired. The present research explored the expression pattern, functional role and underlying mechanism of DLX6-AS1 in GC. Firstly, we measured DLX6-AS1 expression in GC and then found the elevated level of DLX6-AS1. To further inspect the function role of DLX6-AS1 involved in GC, we performed lost-of-function assays. The silencing of DLX6-AS1 suppressed cell proliferation, migration and EMT process of GC cells. Subsequently, we uncovered that MAP4K1 was also up-regulated in GC and could be positively regulated by DLX6-AS1. Moreover, MAP4K1 down-regulation similarly inhibited GC progression. In addition, DLX6-AS1 stabilized MAP4K1 via modulating FUS. In summary, DLX6-AS1 modulated GC progression through FUS-regulated MAP4K1. Our paper exposed the role and regulatory mechanism of DLX6-AS1 in GC, which suggested a novel and valid therapy for GC patients.
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Affiliation(s)
- Qiong Wu
- Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiali Ma
- Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wenying Meng
- Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Pingping Hui
- Department of Gastroenterology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Chen X, Tan XR, Li SJ, Zhang XX. LncRNA NEAT1 promotes hepatic lipid accumulation via regulating miR-146a-5p/ROCK1 in nonalcoholic fatty liver disease. Life Sci 2019; 235:116829. [PMID: 31484042 DOI: 10.1016/j.lfs.2019.116829] [Citation(s) in RCA: 78] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Revised: 08/26/2019] [Accepted: 08/31/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a severe liver disease, which influences the health of people worldwide. However, the specific mechanism of the disease remains unknown, and effective treatments are still lacking. It was reported that Nuclear enriched abundant transcript 1 (NEAT1) obviously was up-regulated in NAFLD model. But the role and underlying mechanism of NEAT1 in NAFLD is unclear. METHODS HepG2 cells were treated by free fatty acids (FFA) and C57BL/6J mice were treated by high-fat diet to establish NAFLD in vitro and in vivo models, respectively. Cell transfection was applied to regulate the expression of NEAT1, ROCK1, and miR-146a-5p. Western blotting and qRT-PCR were used for measuring expression of protein and mRNA level, respectively. Dual luciferase assay was used to detect the target relationship. Oil Red O staining was used to measure the lipid accumulation. HE staining was used for observing pathological feature of liver tissues. RESULTS High levels of NEAT1 and ROCK1, and low level of miR-146a-5p were identified in NAFLD models. NEAT1 could target miR-146a-5p to promote ROCK1 expression. Knockdown of NEAT1, overexpression of miR-146a-5p and knockdown of ROCK1 inhibited lipid accumulation through activating AMPK pathway. CONCLUSION NEAT1 may regulate NAFLD through miR-146a-5p targeting ROCK1, and further affect AMPK/SREBP pathway. This study may provide a new thought for the treatment of NAFLD.
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Affiliation(s)
- Xi Chen
- Department of Pediatrics, The Second Xiangya Hospital, Central South Univeristy, Changsha 410011, Hunan Province, PR China
| | - Xin-Rui Tan
- Department of Pediatrics, The Second Xiangya Hospital, Central South Univeristy, Changsha 410011, Hunan Province, PR China
| | - Shi-Jun Li
- Department of Pediatrics, The Second Xiangya Hospital, Central South Univeristy, Changsha 410011, Hunan Province, PR China
| | - Xing-Xing Zhang
- Department of Pediatrics, The Second Xiangya Hospital, Central South Univeristy, Changsha 410011, Hunan Province, PR China.
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Sun Y, Song Y, Liu C, Geng J. LncRNA NEAT1-MicroRNA-140 axis exacerbates nonalcoholic fatty liver through interrupting AMPK/SREBP-1 signaling. Biochem Biophys Res Commun 2019; 516:584-590. [PMID: 31239155 DOI: 10.1016/j.bbrc.2019.06.104] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2019] [Accepted: 06/18/2019] [Indexed: 12/25/2022]
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is a severe liver disease, which influences the health of people worldwide. However, the mechanism modulating the pathogenesis of NAFLD remains elusive. It was reported that nuclear enriched abundant transcript 1 (NEAT1) and microRNA-140 (miR-140) could regulate lipogenesis, but whether they could influence NAFLD are still unknown. METHODS HepG2 cells were treated by free fatty acids (FFA) to establish the model of NAFLD in vitro, and C57 mice were treated by high-fat diet to establish the model of NAFLD in vivo. Cell transfection was applied to regulate the expression of NEAT1 and miR-140. Western blotting and qRT-PCR were applied for measuring expression of protein and mRNA, respectively. HE staining and Oil Red O staining were used for observing liver tissues. RESULTS NEAT1 and miR-140 are upregulated in hepacytes under the NAFLD conditions. NEAT1 directly binds to miR-140 and acts synergistically with miR-140 to exacerbate the progression of NAFLD. Reciprocally, silence of miR-140 or NEAT1 alleviates the severity of NAFLD. The mechanistical study shows that the axis of NEAT1-miR-140 inactivates AMPK/SREBP-1 signaling during the NAFLD. . CONCLUSION The NEAT1-miR-140 axis play a crucial role in modulation of NAFLD via inactivation of AMPK/SREBP1 signaling. This study may provide a novel insight for the treatment of NAFLD.
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Affiliation(s)
- Yunfu Sun
- Department of Hepatobiliary Surgery, Weihai Municipal Hospital Affiliated to Dalian Medical University, Weihai, China.
| | - Yu Song
- Department of Hepatobiliary Surgery, Weihai Municipal Hospital Affiliated to Dalian Medical University, Weihai, China
| | - Changsheng Liu
- The Second Department of General Surgery, Southern Ward of Weihai Municipal Hospital Affiliated to Dalian Medical University, Weihai, China
| | - Jianli Geng
- Department of Hepatobiliary Surgery, Weihai Municipal Hospital Affiliated to Dalian Medical University, Weihai, China
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Shaker OG, Abdelwahed MY, Ahmed NA, Hassan EA, Ahmed TI, Abousarie MA, Ayoub SE. Evaluation of serum long noncoding RNA NEAT and MiR-129-5p in hepatocellular carcinoma. IUBMB Life 2019; 71:1571-1578. [PMID: 31190421 DOI: 10.1002/iub.2096] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Accepted: 05/21/2019] [Indexed: 12/26/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the most prevalent form of cancer. Various long non coding RNA (lncRNAs) and micro RNA have been confirmed to have a role in the progression of HCC. Our aim was to investigate for the first time the expression profile of serum level of LNC NEAT (nuclear enrich abundant transcript) and MiR-129-5p in HCC patients and their relations with patient's clinical and biochemical investigations rather than previous studies on tissue cell lines. Our study includes 72 subjects divided into 36 as control subjects and 36 patients with HCC. Complete physical and laboratory investigations were done on all subjects. RNAs were extracted from sera of all subjects. RNAs were reversed transcribed into cDNAs using Qiagen, Valenica, CA. Quantitative PCR (qPCR) was performed using Rotor gene Q System (Qiagen). Relative NEAT1 expression level was significantly increased in serum of HCC patients 4.7 (1.31-6.82) (p < .0001). Meanwhile MiR-129-5p relative expression level was significantly decreased in serum of HCC patients 0.17 (0.14-20) (p < .0001). Also there was negative significant correlation between the expression level of LNC NEAT and MiR-129-5p in HCC group (p < .0001). ROC curve analysis revealed that LNC NEAT; AUC = 0.981, p < .0001, cutoff value (1.02), sensitivity 100%, specificity 88.9%. MiR-129-5p; AUC = 0.997, p < .0001, cutoff value (0.43), sensitivity 100%, specificity 97.2%. Serum LNC NEAT and MiR-129-5p could be used as potential biomarkers for HCC cancer diagnosis and prognosis.
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Affiliation(s)
- Olfat G Shaker
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Mostafa Y Abdelwahed
- Department of Physiology, Faculty of Medicine, Fayoum University, Al Fayoum, Egypt
| | - Naglaa A Ahmed
- Department of Physiology, Faculty of Medicine, Zagazig University, ElZagazig, Egypt
| | - Essam A Hassan
- Department of Tropical Medicine, Fayoum University, Al Fayoum, Egypt
| | - Tarek I Ahmed
- Department of Internal Medicine, Fayoum University, Al Fayoum, Egypt
| | | | - Shymaa E Ayoub
- Department of Biochemistry, Fayoum University, Al Fayoum, Egypt
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Huang R, Duan X, Fan J, Li G, Wang B. Role of Noncoding RNA in Development of Nonalcoholic Fatty Liver Disease. BIOMED RESEARCH INTERNATIONAL 2019; 2019:8690592. [PMID: 30931332 PMCID: PMC6413411 DOI: 10.1155/2019/8690592] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Accepted: 02/13/2019] [Indexed: 12/13/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence globally, but little is known about its specific molecular mechanisms. During the past decade, noncoding RNAs (ncRNAs) have been linked to NAFLD initiation and progression. They are a class of RNAs that play an important role in regulating gene expression despite not encoding proteins. This review summarizes recent research on the relationship between ncRNAs and NAFLD. We discussed the potential applicability of ncRNAs as a biomarker for early NAFLD diagnosis and assessment of disease severity. With further study, ncRNAs should prove to be valuable new targets for NAFLD treatment and benefit the development of noninvasive diagnostic methods.
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Affiliation(s)
- Ruixian Huang
- Center for Fatty Liver, Department of Gastroenterology, Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Xiaoyan Duan
- Center for Fatty Liver, Department of Gastroenterology, Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Jangao Fan
- Center for Fatty Liver, Department of Gastroenterology, Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Guangming Li
- Center for Fatty Liver, Department of Gastroenterology, Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
| | - Baocan Wang
- Center for Fatty Liver, Department of Gastroenterology, Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
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Zhu L, Yang N, Li C, Liu G, Pan W, Li X. Long noncoding RNA NEAT1 promotes cell proliferation, migration, and invasion in hepatocellular carcinoma through interacting with miR-384. J Cell Biochem 2019; 120:1997-2006. [PMID: 30346062 PMCID: PMC6587825 DOI: 10.1002/jcb.27499] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2018] [Accepted: 07/25/2018] [Indexed: 01/24/2023]
Abstract
It was reported that long non-coding RNA nuclear-enriched abundant transcript 1 (NEAT1) is involved in hepatocellular carcinoma (HCC). However, the underlying mechanism of tumorigenesis is still largely unclear. Here, we found that NEAT1 is remarkably upregulated in HCC tissues and cell lines. Overexpression of NEAT1 notably accelerated HCC cell proliferation, migration, and invasion. Knockdown of NEAT1 significantly inhibited HCC cell proliferation, migration and invasion. MiR-384 expression was lower in HCC tissues and cell lines than adjacent nontumor tissues and L02 cell. MiR-384 exhibited the functions of tumor-suppressive. The expression of miR-384 was negatively correlated with the expression of NEAT1. Overexpression of NEAT1 reduced miR-384 expression, whereas inhibition of miR-384 led to a distinct upregulation of NEAT1 expression. In addition, we provided evidence that miR-384 was directly bound to the sequence of NEAT1 by luciferase reporter and RNA-binding protein immunoprecipitation assays. Overexpression of miR-384 inhibited NEAT1 function. Thus, we demonstrated that NEAT1 promotes the malignant biological properties of hepatocellular carcinoma by negatively regulating miR-384.
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Affiliation(s)
- Liying Zhu
- Department of Medical LaboratoryAffiliated Hospital of Guizhou Medical UniversityGuiyangGuizhouChina,Department of Medical LaboratoryGuizhou Medical UniversityGuiyangGuizhouChina
| | - Nenghong Yang
- Department of Hepatobiliary SurgeryAffiliated Hospital of Guizhou Medical UniversityChina
| | - Chengcheng Li
- Department of Hepatobiliary SurgeryAffiliated Hospital of Guizhou Medical UniversityChina
| | - Guoqi Liu
- Department of Medical LaboratoryGuizhou Medical UniversityGuiyangGuizhouChina
| | - Wei Pan
- Department of Medical LaboratoryAffiliated Hospital of Guizhou Medical UniversityGuiyangGuizhouChina,Department of Medical LaboratoryGuizhou Medical UniversityGuiyangGuizhouChina,Prenatal Diagnosis Center, Affiliated Hospital of Guizhou Medical University and Guizhou Provincial Prenatal Diagnosis Center
| | - Xing Li
- Department of Medical LaboratoryAffiliated Hospital of Guizhou Medical UniversityGuiyangGuizhouChina,Department of Medical LaboratoryGuizhou Medical UniversityGuiyangGuizhouChina
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Tan HY, Wang C, Liu G, Zhou X. Long noncoding RNA NEAT1-modulated miR-506 regulates gastric cancer development through targeting STAT3. J Cell Biochem 2019; 120:4827-4836. [PMID: 29363783 DOI: 10.1002/jcb.26691] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Accepted: 01/22/2018] [Indexed: 12/27/2022]
Abstract
Accumulating evidence has indicated that long noncoding RNA NEAT1 exerts critical roles in cancers. So far, the detailed biological role and mechanisms of NEAT1, which are responsible for human gastric cancer (GC), are still largely unknown. Here, we observed that NEAT1 and STAT3 expressions were significantly upregulated in human GC cells including BGC823, SGC-7901, AGS, MGC803, and MKN28 cells compared with normal gastric epithelial cells GES-1, while miR-506 was downregulated. We inhibited NEAT1 and observed that NEAT1 inhibition was able to repress the growth, migration, and invasion of GC cells. Conversely, overexpression of NEAT1 exhibited an increased ability of GC progression in BGC823 and SGC-7901 cells. Bioinformatics analysis, dual luciferase reporter assays, RIP assays, and RNA pull-down tests validated the negative binding correlation between NEAT1 and miR-506. In addition, it was found that miR-506 can modulate the expression of NEAT1 in vitro. STAT3 was predicted as a messenger RNA (mRNA) target of miR-506, and miR-506 mimics can suppress STAT3 mRNA expression. Subsequently, it was observed that downregulation of NEAT1 can restrain GC development by decreasing STAT3, which can be reversed by miR-506 inhibitors. Therefore, it was hypothesized in our study that NEAT1 can be recognized as a competing endogenous RNA to modulate STAT3 by sponging miR-506 in GC. In conclusion, we implied that NEAT1 can serve as an important biomarker in GC diagnosis and treatment.
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Affiliation(s)
- Hai-Yang Tan
- Department of Gastrointestinal Surgery, The First People's Hospital of Tianmen, Tianmen, Hubei, China
| | - Changcheng Wang
- Department of Gastroenterology, Huai'an Second People's Hospital, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, Jiangsu, China
| | - Gao Liu
- Department of Gastrointestinal Surgery, Central Hospital of Enshi Autonomous Prefecture, Enshi Clinical College of Wuhan University, Enshi, Hubei, China
| | - Xiang Zhou
- Department of Rehabilitation, Huai'an Second People's Hospital, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, Jiangsu, China
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40
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Liu Z, Wu K, Wu J, Tian D, Chen Y, Yang Z, Wu A. NEAT1 is a potential prognostic biomarker for patients with nasopharyngeal carcinoma. J Cell Biochem 2019; 120:9831-9838. [PMID: 30618186 DOI: 10.1002/jcb.28263] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2018] [Accepted: 10/22/2018] [Indexed: 01/14/2023]
Abstract
Nuclear paraspeckle assembly transcript 1 (NEAT1) has been found to be dysregulated and associated with clinical progression in various human cancers. The clinical and prognostic value of NEAT1 in nasopharyngeal carcinoma (NPC) was still controversial. The aim of our study was to provide more sufficient evidence that NEAT1 expression is correlated with overall survival in patients with NPC. NEAT1 expression was detected in NPC tissue samples, and the relationship between NEAT1 expression and clinical parameters, including prognosis, was analyzed. The meta-analysis was performed to further assess the prognostic significance of NEAT1 expression in patients with NPC. In our study, we found that the levels of NEAT1 expression were increased in NPC clinical tissue specimens, and associated with advanced M classification and clinical stages. Moreover, the Kaplan-Meier analysis suggested that the levels of NEAT1 expression were negatively associated with the overall survival of patients with NPC. Furthermore, univariate and multivariate Cox regression analyses showed that NEAT1 high-expression was an independent unfavorable prognostic factor in patients with NPC. Finally, we conducted a meta-analysis including 297 patients with NPC from the three studies, and found the pooled HR (95% confidence interval [CI]) was 1.64 (95% CI: 0.68-3.93) for the random effects model and 2.04 (95% CI: 1.42-2.95) for the fixed effect model. In conclusion, NEAT1 is a potential prognostic biomarker for NPC, but more studies are needed to further verify the prognostic value of NEAT1 in patients with NPC.
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Affiliation(s)
- Zhuoxing Liu
- Department of Oncology, Heyuan People's Hospital, Affiliated Heyuan Hospital of Jinan University, Heyuan, Guangdong, China
| | - Kunpeng Wu
- Department of Oncology, Heyuan People's Hospital, Affiliated Heyuan Hospital of Jinan University, Heyuan, Guangdong, China
| | - Jian Wu
- Department of Oncology, Heyuan People's Hospital, Affiliated Heyuan Hospital of Jinan University, Heyuan, Guangdong, China
| | - Dan Tian
- Department of Oncology, Heyuan People's Hospital, Affiliated Heyuan Hospital of Jinan University, Heyuan, Guangdong, China
| | - Yue Chen
- Department of Oncology, Heyuan People's Hospital, Affiliated Heyuan Hospital of Jinan University, Heyuan, Guangdong, China
| | - Zhixiong Yang
- Department of Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Aibing Wu
- Department of Oncology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong, China
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Zhu Z, Du S, Yin K, Ai S, Yu M, Liu Y, Shen Y, Liu M, Jiao R, Chen X, Guan W. Knockdown long noncoding RNA nuclear paraspeckle assembly transcript 1 suppresses colorectal cancer through modulating miR-193a-3p/KRAS. Cancer Med 2019; 8:261-275. [PMID: 30575330 PMCID: PMC6346262 DOI: 10.1002/cam4.1798] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2018] [Revised: 08/24/2018] [Accepted: 09/03/2018] [Indexed: 12/20/2022] Open
Abstract
The nuclear paraspeckle assembly transcript 1 (abbreviated as NEAT1), a nuclear sufficient long noncoding RNA (abbreviated as lncRNA), has aroused a rising concern in recent years. As uncovered by reports, the increase in NEAT1 is related to the deteriorated prognosis of lung cancer, breast cancer, hepatocellular cancer, and colorectal cancer (abbreviated as CRC). Thus far, the mechanism of NEAT1 has not been elucidated by the existing researches. The impact of knockdown of both NEAT1 and its predicted downstream miR-193a-3p in CRC cells was examined here to delve into their interactions and mechanisms. Additionally, the target of miR-193a-3p, Kirsten rat sarcoma viral oncogene homolog (abbreviated as KRAS), was also predicted by bioinformatics algorithms. Small interfering RNA and antisense oligonucleotides that inhibit NEAT1, as well as overexpression or knockdown of miR-193a-3p, were adequately drawn upon to confirm that NEAT1 serves as a miR-193a-3p sponge or competing endogenous RNA, to impact miR-193a-3p's further functions, including modulating KRAS proteins, both in vitro and in vivo. Generally, lncRNA NEAT1/hsa-miR-193a-3p/KRAS axis was substantiated in CRC cells and could provide novel insight into both diagnostic and therapeutic advancement in CRC.
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Affiliation(s)
- Zhouting Zhu
- Department of General SurgeryAffiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingChina
- State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life SciencesNanjing UniversityNanjingChina
| | - Shangce Du
- Department of General SurgeryDrum Tower Clinical Medical College of Nanjing Medical UniversityNanjingChina
| | - Kai Yin
- Department of General SurgeryTaixing Hospital Affiliated to Yangzhou UniversityTaixingChina
| | - Shichao Ai
- Department of General SurgeryAffiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingChina
| | - Mengchao Yu
- State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life SciencesNanjing UniversityNanjingChina
| | - Yanqing Liu
- State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life SciencesNanjing UniversityNanjingChina
| | - Yan Shen
- Department of General SurgeryAffiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingChina
| | - Minghui Liu
- State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life SciencesNanjing UniversityNanjingChina
| | - Ruihua Jiao
- State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life SciencesNanjing UniversityNanjingChina
| | - Xi Chen
- State Key Laboratory of Pharmaceutical Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, School of Life SciencesNanjing UniversityNanjingChina
| | - Wenxian Guan
- Department of General SurgeryAffiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingChina
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Wu F, Mo Q, Wan X, Dan J, Hu H. NEAT1/hsa-mir-98-5p/MAPK6 axis is involved in non-small-cell lung cancer development. J Cell Biochem 2018; 120:2836-2846. [PMID: 29095526 DOI: 10.1002/jcb.26442] [Citation(s) in RCA: 62] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Revised: 09/20/2017] [Accepted: 10/03/2017] [Indexed: 12/20/2022]
Abstract
Long noncoding RNAs (lncRNAs) or microRNAs belong to the two most important noncoding RNAs and they are involved in a lot of cancers, including non-small-cell lung cancer (NSCLC). Therefore, currently, we focused on the biological and clinical significance of lncRNA nuclear enriched abundant transcript 1 (NEAT1) and hsa-mir-98-5p in NSCLC. It was observed that NEAT1 was upregulated while hsa-mir-98-5p was downregulated respectively in NSCLC cell lines compared to human normal lung epithelial BES-2B cells. Inhibition of NEAT1 can suppress the progression of NSCLC cells and hsa-mir-98-5p can reverse this phenomenon. Bioinformatics search was used to elucidate the correlation between NEAT1 and hsa-mir-98-5p. Additionally, a novel messenger RNA target of hsa-mir-98-5p, mitogen-activated protein kinase 6 (MAPK6), was predicted. Overexpression and knockdown studies were conducted to verify whether NEAT1 exhibits its biological functions through regulating hsa-mir-98-5p and MAPK6 in vitro. NEAT1 was able to increase MAPK6 expression and hsa-mir-98-5p mimics can inhibit MAPK6 via downregulating NEAT1 levels. We speculated that NEAT1 may act as a competing endogenous lncRNA to upregulate MAPK6 by attaching hsa-mir-98-5p in lung cancers. Taken these together, NEAT1/hsa-mir-98-5p/MAPK6 is involved in the development and progress in NSCLC. NEAT1 could be recommended as a prognostic biomarker and therapeutic indicator in NSCLC diagnosis and treatment.
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Affiliation(s)
- Feima Wu
- Department of Cardiothoracic Surgery, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, China
| | - Qiang Mo
- Department of Emergency, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, China
| | - Xiaoling Wan
- Department of Emergency, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, China
| | - Jialong Dan
- Department of ICU, Xianning Central Hospital, The First Affiliated Hospital of Hubei University of Science and Technology, Xianning, China
| | - Haibo Hu
- Department of Thoracic Surgery, Huai'an Second People's Hospital, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China
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Yang X, Qu S, Wang L, Zhang H, Yang Z, Wang J, Dai B, Tao K, Shang R, Liu Z, Li X, Zhang Z, Xia C, Ma B, Liu W, Li H, Dou K. PTBP3 splicing factor promotes hepatocellular carcinoma by destroying the splicing balance of NEAT1 and pre-miR-612. Oncogene 2018; 37:6399-6413. [PMID: 30068940 DOI: 10.1038/s41388-018-0416-8] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2017] [Revised: 05/31/2018] [Accepted: 06/29/2018] [Indexed: 12/13/2022]
Abstract
Nuclear-enriched RNA-binding proteins (RBPs) are mainly involved in transcriptional regulation, which is a critical checkpoint to tune gene diversity and expression levels. We analyzed nuclear RBPs in human HCC tissues and matched normal control tissues. Based on the gene expression levels, PTBP3 was identified as top-ranked in the nuclei of HCC cells. HCC cell lines then were transfected with siRNAs or lentiviral vectors. PTBP3 promoted HCC cell proliferation and metastasis both in vitro and in vivo. RNA immunoprecipitation (RIP), fluorescence in situ hybridization (FISH) and qRT-PCR assays verified that PTBP3 protein recruited abundant lnc-NEAT1 splicing variants (NEAT1_1 and NEAT1_2) and pre-miR-612 (precursor of miR-612) in the nucleus. NEAT1_1, NEAT1_2 and miR-612 expression levels were determined by PTBP3. Correlational analyses revealed that PTBP3 was positively correlated with NEAT1, but it was inversely correlated with miR-612 in HCC. The P53/CCND1 and AKT2/EMT pathways were determined by NEAT1 and miR-612 respectively in HCC. The PTBP3high and NEAT1high/miR-612low patients had a shorter overall survival. Therefore, nuclear-enriched RBP, PTBP3, promotes HCC cell malignant growth and metastasis by regulating the balance of splicing variants (NEAT1_1, NEAT1_2 and miR-612) in HCC.
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Affiliation(s)
- Xisheng Yang
- Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China
| | - Shibin Qu
- Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China.,Section of General Surgery, Department of Surgery, University of Michigan, Ann Arbor, Michigan, USA
| | - Lin Wang
- Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China
| | - Hongtao Zhang
- Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China
| | - Zhaoxu Yang
- Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China
| | - Jianlin Wang
- Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China
| | - Bin Dai
- Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China
| | - Kaishan Tao
- Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China
| | - Runze Shang
- Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China
| | - Zhengcai Liu
- Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China
| | - Xiao Li
- Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China
| | - Zhuochao Zhang
- Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China
| | - Congcong Xia
- Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China
| | - Ben Ma
- Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China
| | - Wei Liu
- Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China
| | - Haimin Li
- Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China.
| | - Kefeng Dou
- Department of Hepatobiliary Surgery, The Xijing Hospital of The Fourth Military Medical University, Xi'an, China.
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Lin YH, Wu MH, Huang YH, Yeh CT, Chi HC, Tsai CY, Chuang WY, Yu CJ, Chung IH, Chen CY, Lin KH. Thyroid hormone negatively regulates tumorigenesis through suppression of BC200. Endocr Relat Cancer 2018; 25:967-979. [PMID: 30400024 DOI: 10.1530/erc-18-0176] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/22/2018] [Accepted: 07/10/2018] [Indexed: 01/06/2023]
Abstract
Thyroid hormone (T3) and its receptor (TR) are involved in cancer progression. While deregulation of long non-coding RNA (lncRNA) expression has been detected in many tumor types, the mechanisms underlying specific involvement of lncRNAs in tumorigenicity remain unclear. Experiments from the current study revealed negative regulation of BC200 expression by T3/TR. BC200 was highly expressed in hepatocellular carcinoma (HCC) and effective as an independent prognostic marker. BC200 promoted cell growth and tumor sphere formation, which was mediated via regulation of cell cycle-related genes and stemness markers. Moreover, BC200 protected cyclin E2 mRNA from degradation. Cell growth ability was repressed by T3, but partially enhanced upon BC200 overexpression. Mechanistically, BC200 directly interacted with cyclin E2 and promoted CDK2-cyclin E2 complex formation. Upregulation of cell cycle-related genes in hepatoma samples was positively correlated with BC200 expression. Our collective findings support the utility of a potential therapeutic strategy involving targeting of BC200 for the treatment of HCC.
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Affiliation(s)
- Yang-Hsiang Lin
- Department of Biochemistry, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
| | - Meng-Han Wu
- Department of Biochemistry, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ya-Hui Huang
- Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
| | - Chau-Ting Yeh
- Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
| | - Hsiang-Cheng Chi
- Department of Biochemistry, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University/Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
| | - Chung-Ying Tsai
- Kidney Research Center and Department of Nephrology, Chang Gung Memorial Hospital, Taoyuan, Taiwan
| | - Wen-Yu Chuang
- Department of Pathology, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Chia-Jung Yu
- Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Cell and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Department of Thoracic Medicine, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
| | - I-Hsiao Chung
- Department of Biochemistry, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ching-Ying Chen
- Department of Biochemistry, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Kwang-Huei Lin
- Department of Biochemistry, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Liver Research Center, Chang Gung Memorial Hospital, Linkou, Taoyuan, Taiwan
- Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan
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Wang L, Xia JW, Ke ZP, Zhang BH. Blockade of NEAT1 represses inflammation response and lipid uptake via modulating miR-342-3p in human macrophages THP-1 cells. J Cell Physiol 2018; 234:5319-5326. [PMID: 30259979 DOI: 10.1002/jcp.27340] [Citation(s) in RCA: 85] [Impact Index Per Article: 12.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Accepted: 08/10/2018] [Indexed: 12/13/2022]
Abstract
Atherosclerosis has been recognized as a chronic inflammation process induced by lipid of the vessel wall. Oxidized low-density lipoprotein (ox-LDL) can drive atherosclerosis progression involving macrophages. Recently, long noncoding RNAs (lncRNAs) have been reported to play critical roles in atherosclerosis development. In our current study, we focused on the biological roles of lncRNA NEAT1 in atherosclerosis progress. Here, we found that ox-LDL was able to trigger human macrophages THP-1 cells, a human monocytic cell line, apoptosis in a dose-dependent and time-dependent course. In addition, we observed that NEAT1 was significantly increased in THP-1 cells incubated with ox-LDL and meanwhile miR-342-3p was greatly decreased. Then, NEAT1 was silenced by transfection of small interfering RNA (siRNA) of NEAT1 into THP-1 cells. As exhibited, CD36, oil-red staining levels, total cholesterol (TC), total cholesterol (TG) levels and THP-1 cell apoptosis were obviously repressed by knockdown of NEAT1. Furthermore, inhibition of NEAT1 contributed to the repression of inflammation in vitro. Interleukin 6 (IL-6), IL-1β, cyclooxygenase-2 (COX-2) and tumour necrosis factor-alpha (TNF-α) protein levels were remarkably depressed by NEAT1 siRNA in THP-1 cells. By using bioinformatics analysis, miR-342-3p was predicted as a downstream target of NEAT1 and the correlation between them was confirmed in our study. Moreover, overexpression of miR-342-3p could also greatly suppress inflammation response and lipid uptake in THP-1 cells. Knockdown of NEAT1 and miR-342-3p mimics inhibited lipid uptake in THP-1 cells. In conclusion, we implied that blockade of NEAT1 repressed inflammation response through modulating miR-342-3p in human macrophages THP-1 cells and NEAT1 may offer a promising strategy to treat atherosclerotic cardiovascular diseases.
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Affiliation(s)
- Lei Wang
- Department of Cardiology, The People's Hospital of China Three Gorges University/The First People's Hospital of Yichang, Yichang, China
| | - Jing-Wen Xia
- Department of Cardiology, Shanghai Songjiang District Center Hospital, Shanghai, China
| | - Zun-Ping Ke
- Department of Cardiology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
| | - Bing-Hong Zhang
- Departments of Neonatology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China
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Huang D, Bi C, Zhao Q, Ding X, Bian C, Wang H, Wang T, Liu H. Knockdown long non-coding RNA ANRIL inhibits proliferation, migration and invasion of HepG2 cells by down-regulation of miR-191. BMC Cancer 2018; 18:919. [PMID: 30249208 PMCID: PMC6154945 DOI: 10.1186/s12885-018-4831-6] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Accepted: 09/18/2018] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a common malignant tumor with high fatality rate. Recent studies reported that up-regulation of long non-coding RNA antisense non-coding RNA in the INK4 locus (lncRNA ANRIL) was found in HCC tissues, and which could affect HCC cells biological processes. However, the potential molecular mechanism of ANRIL in HCC is still unclear. The study aimed to uncover the effect of ANRIL on HepG2 cells growth, migration and invasion. METHODS The knockdown expression vectors of ANRIL were transfected into HepG2 cells, and qRT-PCR, CCK-8, flow cytometry, Transwell and western blot assays were performed to analyze the effect of ANRIL on cell proliferation, apoptosis, migration and invasion. The relative expression of miR-191 was then examined in ANRIL knockdown vector transfected cells. These experiments were repeated again for exploring the effect of miR-191 on HepG2 cells. NF-κB and Wnt/β-catenin signaling pathways were examined by using western blot assay. RESULTS Knockdown of ANRIL inhibited proliferation, induced apoptosis, meanwhile suppressed migration and invasion of HepG2 cells. Additionally, the results showed that the expression level of miR-191 was down-regulated by ANRIL knockdown in HepG2 cells. Importantly, overexpression of miR-191 reversed the anti-tumor effect of ANRIL on cell proliferation, apoptosis, migration and invasion in HepG2 cells. Besides, we found that ANRIL knockdown inactivated NF-κB and Wnt/β-catenin pathways by regulating miR-191. CONCLUSIONS These data demonstrated that ANRIL knockdown suppressed proliferation, migration, invasion, and promoted apoptosis in HepG2 cells by down-regulating miR-191 and inactivating NF-κB and Wnt/β-catenin signaling pathways.
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Affiliation(s)
- Deyu Huang
- Department of Infectious Disease, The Affiliated Hospital of Qingdao University, Qingdao, 266003 Shandong China
| | - Chunhua Bi
- Department of Infectious Disease, The Affiliated Hospital of Qingdao University, Qingdao, 266003 Shandong China
| | - Qingxi Zhao
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, No.16, Jiangsu Road, Qingdao, 266003 Shandong China
| | - Xueli Ding
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, No.16, Jiangsu Road, Qingdao, 266003 Shandong China
| | - Cheng Bian
- Department of Infectious Disease, The Affiliated Hospital of Qingdao University, Qingdao, 266003 Shandong China
| | - Hui Wang
- Department of Infectious Disease, The Affiliated Hospital of Qingdao University, Qingdao, 266003 Shandong China
| | - Ting Wang
- Department of Infectious Disease, The Affiliated Hospital of Qingdao University, Qingdao, 266003 Shandong China
| | - Hua Liu
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University, No.16, Jiangsu Road, Qingdao, 266003 Shandong China
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The Role of Long Non-Coding RNAs (lncRNAs) in the Development and Progression of Fibrosis Associated with Nonalcoholic Fatty Liver Disease (NAFLD). Noncoding RNA 2018; 4:ncrna4030018. [PMID: 30134610 PMCID: PMC6162709 DOI: 10.3390/ncrna4030018] [Citation(s) in RCA: 35] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Revised: 08/14/2018] [Accepted: 08/17/2018] [Indexed: 12/11/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) encompasses a spectrum of conditions ranging from hepatic steatosis to inflammation (nonalcoholic steatohepatitis or NASH) with or without fibrosis, in the absence of significant alcohol consumption. The presence of fibrosis in NASH patients is associated with greater liver-related morbidity and mortality; however, the molecular mechanisms underlying the development of fibrosis and cirrhosis in NAFLD patients remain poorly understood. Long non-coding RNAs (lncRNAs) are emerging as key contributors to biological processes that are underpinning the initiation and progression of NAFLD fibrosis. This review summarizes the experimental findings that have been obtained to date in animal models of liver fibrosis and NAFLD patients with fibrosis. We also discuss the potential applicability of circulating lncRNAs to serve as biomarkers for the diagnosis and prognosis of NAFLD fibrosis. A better understanding of the role played by lncRNAs in NAFLD fibrosis is critical for the identification of novel therapeutic targets for drug development and improved, noninvasive methods for disease diagnosis.
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Peng L, Yuan XQ, Zhang CY, Peng JY, Zhang YQ, Pan X, Li GC. The emergence of long non-coding RNAs in hepatocellular carcinoma: an update. J Cancer 2018; 9:2549-2558. [PMID: 30026854 PMCID: PMC6036883 DOI: 10.7150/jca.24560] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2017] [Accepted: 03/31/2018] [Indexed: 12/11/2022] Open
Abstract
Hepatocellular carcinoma (HCC) accounting for roughly 90% of all primary liver neoplasms is the sixth most frequent neoplasm and the second prominent reason of tumor fatality worldwide. As regulators of diverse biological processes, long non-coding RNAs (lncRNAs) are involved in onset and development of neoplasms. With the continuous booming of well-featured lncRNAs in HCC from 2016 to now, we reviewed the newly-presented comprehension about the relationship between lncRNAs and HCC in this study. To be specific, we summarized the overview function and study tools of lncRNAs, elaborated the roles of lncRNAs in HCC, and sketched the molecule mechanisms of lncRNAs in HCC. In addition, the application of lncRNAs serving as biomarkers in early diagnosis and outcome prediction of HCC patients was highlighted.
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Affiliation(s)
- Li Peng
- Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha 410078, P.R. China; Cancer Research Institute, Central South University, Changsha 410078, P.R. China
- Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P.R. China
| | - Xiao-Qing Yuan
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
- Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China
| | - Chao-Yang Zhang
- Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha 410078, P.R. China; Cancer Research Institute, Central South University, Changsha 410078, P.R. China
| | - Jiang-Yun Peng
- Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P.R. China
| | - Ya-Qin Zhang
- Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha 410078, P.R. China; Cancer Research Institute, Central South University, Changsha 410078, P.R. China
| | - Xi Pan
- Department of Oncology, the third Xiangya Hospital, Central South University, Changsha 410013, P.R. China
| | - Guan-Cheng Li
- Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha 410078, P.R. China; Cancer Research Institute, Central South University, Changsha 410078, P.R. China
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lncAKHE enhances cell growth and migration in hepatocellular carcinoma via activation of NOTCH2 signaling. Cell Death Dis 2018; 9:487. [PMID: 29706630 PMCID: PMC5924759 DOI: 10.1038/s41419-018-0554-5] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Revised: 03/02/2018] [Accepted: 03/09/2018] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma is the sixth most common cancer and gives rise to numerous deaths around the world every year. However, the molecular mechanism that controls hepatocarcinogenesis remains largely unknown. Here we found out an uncharacterized long noncoding RNA named lncAKHE. We found that lncAKHE was highly expressed in hepatocellular carcinoma tissues. lncAKHE depletion remarkably impaired the abilities of cell proliferation, migration, and invasion in hepatocellular carcinoma while promgoogoting cell apoptosis. Moreover, higher expression level of lncAKHE in hepatocellular carcinoma tissues was associated with more clinical severity and lower survival rates. Mechanistically, lncAKHE cooperated with YEATS4 to enhance the activation of NOTCH2 signaling which is usually abnormally upregulated in hepatocellular carcinoma. In conclusions, our study showed that lncAKHE may promote tumor progression in HCC and serve as a novel target for HCC treatment.
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Huang X, Gao Y, Qin J, Lu S. lncRNA MIAT promotes proliferation and invasion of HCC cells via sponging miR-214. Am J Physiol Gastrointest Liver Physiol 2018; 314:G559-G565. [PMID: 29097358 DOI: 10.1152/ajpgi.00242.2017] [Citation(s) in RCA: 87] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
The aberrant expression of long noncoding RNAs (lncRNAs) has been involved in various human tumors including hepatocellular carcinoma (HCC). Our study aimed to investigate the potential molecular mechanism of lncRNA myocardial infarction-associated transcript (MIAT) in HCC. The expression of MIAT and micro-RNA (miR)-214 in HCC tissues and cells was examined by quantitative real-time PCR, and the levels of enhancer of zeste homolog 2 (EZH2) and β-catenin were detected by Western blot assay. Immunoprecipitation analysis was used to detect the level of H3/H4 histone acetylation. RNA pull-down assay was performed to confirm the targeting regulatory relationship between miR-214 and MIAT. Cell viability, proliferation, and invasion were analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), [3H]thymidine incorporation, and Transwell assays, respectively. BALB/c nude mice were used to establish a hepatocellular carcinoma animal model with subcutaneous injection of SK-HEP-1 cells. Upregulation of MIAT is related to the proliferation and invasion of HCC, and downregulating MIAT expression inhibited HCC cell proliferation and invasion. The H3/H4 histone acetylation level of MIAT promoter in HCC tissues was higher than that in normal tissues. MIAT negatively regulated miR-214 in HCC cells. Inhibition of miR-214 reversed the influence of MIAT downregulation on HCC cell proliferation and invasion. In nude mouse xenograft models, downregulation of MIAT markedly suppressed the tumor growth of HCC via releasing miR-214. In conclusion, lncRNA MIAT promotes the proliferation and invasion of HCC cells through sponging miR-214, which brings a novel target for the therapy and prognosis of hepatocellular carcinoma. NEW & NOTEWORTHY This is the first research showing long noncoding RNA (lncRNA) myocardial infarction-associated transcript (MIAT) to have a regulatory effect on hepatocellular carcinoma. Micro-RNA (miR)-214 could be sponged by MIAT to promote the proliferation and invasion of hepatocellular carcinoma cells. The lncRNA MIAT/miR-214 axis brings a novel insight for the therapy and prognosis of hepatocellular carcinoma.
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Affiliation(s)
- Xinli Huang
- The Key Laboratory of Living Donor Liver Transplantation, Center of Liver Transplantation, Ministry of Health, The First Affiliated Hospital of Nanjing Medical University , Nanjing , People's Republic of China
| | - Yun Gao
- The Key Laboratory of Living Donor Liver Transplantation, Center of Liver Transplantation, Ministry of Health, The First Affiliated Hospital of Nanjing Medical University , Nanjing , People's Republic of China
| | - Jianjie Qin
- The Key Laboratory of Living Donor Liver Transplantation, Center of Liver Transplantation, Ministry of Health, The First Affiliated Hospital of Nanjing Medical University , Nanjing , People's Republic of China
| | - Sen Lu
- The Key Laboratory of Living Donor Liver Transplantation, Center of Liver Transplantation, Ministry of Health, The First Affiliated Hospital of Nanjing Medical University , Nanjing , People's Republic of China
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