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Tsai CC, Wang CY, Chang HH, Chang PTS, Chang CH, Chu TY, Hsu PC, Kuo CY. Diagnostics and Therapy for Malignant Tumors. Biomedicines 2024; 12:2659. [PMID: 39767566 PMCID: PMC11726849 DOI: 10.3390/biomedicines12122659] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2024] [Revised: 11/20/2024] [Accepted: 11/20/2024] [Indexed: 01/03/2025] Open
Abstract
Malignant tumors remain one of the most significant global health challenges and contribute to high mortality rates across various cancer types. The complex nature of these tumors requires multifaceted diagnostic and therapeutic approaches. This review explores current advancements in diagnostic methods, including molecular imaging, biomarkers, and liquid biopsies. It also delves into the evolution of therapeutic strategies, including surgery, chemotherapy, radiation therapy, and novel targeted therapies such as immunotherapy and gene therapy. Although significant progress has been made in the understanding of cancer biology, the future of oncology lies in the integration of precision medicine, improved diagnostic tools, and personalized therapeutic approaches that address tumor heterogeneity. This review aims to provide a comprehensive overview of the current state of cancer diagnostics and treatments while highlighting emerging trends and challenges that lie ahead.
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Affiliation(s)
- Chung-Che Tsai
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan; (C.-C.T.); (C.-H.C.); (T.Y.C.)
| | - Chun-Yu Wang
- Department of Dentistry, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan;
| | - Hsu-Hung Chang
- Division of Nephrology, Department of Internal Medicine, Sijhih Cathay General Hospital, New Taipei City 221, Taiwan;
| | | | - Chuan-Hsin Chang
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan; (C.-C.T.); (C.-H.C.); (T.Y.C.)
| | - Tin Yi Chu
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan; (C.-C.T.); (C.-H.C.); (T.Y.C.)
| | - Po-Chih Hsu
- Department of Dentistry, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan;
- Institute of Oral Medicine and Materials, College of Medicine, Tzu Chi University, Hualien 970, Taiwan
| | - Chan-Yen Kuo
- Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 231, Taiwan; (C.-C.T.); (C.-H.C.); (T.Y.C.)
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Abam F, Ghorbian S. The dual role of LncRNAs in hepatocellular carcinoma: Friend and foe. GASTROENTEROLOGY & ENDOSCOPY 2024; 2:186-195. [DOI: 10.1016/j.gande.2024.06.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/15/2025]
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Wang H, Chen JJ, Yin SY, Sheng X, Wang HX, Lau WY, Dong H, Cong WM. A Grading System of Microvascular Invasion for Patients with Hepatocellular Carcinoma Undergoing Liver Resection with Curative Intent: A Multicenter Study. J Hepatocell Carcinoma 2024; 11:191-206. [PMID: 38283692 PMCID: PMC10822140 DOI: 10.2147/jhc.s447731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 01/15/2024] [Indexed: 01/30/2024] Open
Abstract
Background Microvascular invasion (MVI) is closely correlated with poor clinical outcomes in patients with hepatocellular carcinoma (HCC). A grading system of MVI is needed to assist in the management of HCC patient. Methods Multicenter data of HCC patients who underwent liver resection with curative intent was analyzed. This grading system was established by detected number and distance from tumor boundary of MVI. Survival outcomes were compared among patients in each group. This system was verified by time-receiver operating characteristic curve, time-area under the curve, calibration curve, and decision curve analyses. Cox regression analysis was performed to study the associated factors of prognosis. Logistic analysis was used to study the predictive factors of MVI. Results All patients were classified into 4 groups: M0: no MVI; M1: 1~5 proximal MVIs (≤1 cm from tumor boundary); M2a: >5 proximal MVIs (≤1 cm from tumor boundary); M2b: ≥1 distal MVIs (>1 cm from tumor boundary). The recurrence-free survival (RFS), overall survival (OS), and early RFS rates among all the individual groups were significantly different. Based on the number of proximal MVI (0~5 vs >5), patients in the M2b group were further divided into two subgroups which also showed different prognosis. Multiple methods showed this grading system to be significantly better than the MVI two-tiered system in prognostic evaluation. Four multivariate models for RFS, OS, early RFS, late RFS, and a predictive model of MVI were then established and were shown to satisfactorily evaluate prognosis and have a great discriminatory power, respectively. Conclusion This MVI grading system could precisely evaluate prognosis of HCC patients after liver resection with curative intent and it could be employed in routine pathological reports. The severity of MVI from both adjacent and distant from tumor boundary should be stated. A hypothesis about two occurrence modes of distal MVI was proposed.
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Affiliation(s)
- Han Wang
- Department of Pathology, Shanghai Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, People’s Republic of China
| | - Jun-Jie Chen
- Department of Radiology, Shanghai Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, People’s Republic of China
| | - Shu-Yi Yin
- Department of Pathology, Shanghai Changhai Hospital, Naval Medical University, Shanghai, People’s Republic of China
| | - Xia Sheng
- Department of Pathology, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China
| | - Hong-Xia Wang
- Department of Pathology, Jiading District Central Hospital, Shanghai University of Medicine & Health Sciences, Shanghai, People’s Republic of China
| | - Wan Yee Lau
- Faculty of Medicine, Chinese University of Hong Kong, Hong Kong, China
| | - Hui Dong
- Department of Pathology, Shanghai Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, People’s Republic of China
| | - Wen-Ming Cong
- Department of Pathology, Shanghai Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, People’s Republic of China
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Bao H, Jiang Y, Wang N, Su H, Han X. Long Noncoding RNAs MALAT1 and HOTTIP Act as Serum Biomarkers for Hepatocellular Carcinoma. Cancer Control 2024; 31:10732748241284821. [PMID: 39259658 PMCID: PMC11406664 DOI: 10.1177/10732748241284821] [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] [Indexed: 09/13/2024] Open
Abstract
BACKGROUND Circulating tumor markers with satisfactory sensitivity and specificity play crucial roles in cancer diagnosis and therapy. This prospective study aimed to evaluate the potential of circulating lncRNAs as biomarkers for hepatocellular carcinoma (HCC). METHODS A total of 74 patients with HCC and 94 healthy controls were enrolled. The expression levels of candidate genes in serum were detected by qRT-PCR. Receiver operating characteristic (ROC) curve analysis and logistic regression were employed to investigate the diagnostic capacity of lncRNAs. The analysis of 3-year overall survival (OS) was conducted using the Kaplan-Meier method and log-rank test. RESULTS Of the 9 candidate genes, 6 lncRNAs could be stably detected in serum. The expression levels of circulating MALAT1 and HOTTIP in HCC patients were significantly higher than those in controls (P < 0.001). ROC analysis showed that MALAT1 and HOTTIP were more effective than alpha-fetoprotein (AFP) (P < 0.010) in the diagnosis of HCC, with AUCs of 0.896 and 0.899, respectively. Additionally, a panel consisting of MALAT1, HOTTIP, and AFP was constructed to obtain an AUC of 0.968 with a sensitivity of 87.8% and specificity of 94.7% in HCC diagnosis. Moreover, the upregulation of MALAT1 was not only related to multiple tumor lesions, HCV infection, AST level, and AFP level, but also suggested shorter OS. A high expression level of HOTTIP was associated with metastasis. CONCLUSION Serum MALAT1 and HOTTIP play indicative roles as non-invasive biomarkers for HCC.
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Affiliation(s)
- Han Bao
- Department of Interventional Radiology, The First Hospital of China Medical University, Shenyang, China
| | - Yutian Jiang
- Department of Interventional Therapy, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China
| | - Ning Wang
- Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Hongying Su
- Department of Interventional Radiology, The First Hospital of China Medical University, Shenyang, China
| | - Xiangjun Han
- Department of Interventional Radiology, The First Hospital of China Medical University, Shenyang, China
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Zhao X, Wang Y, Xia H, Liu S, Huang Z, He R, Yu L, Meng N, Wang H, You J, Li J, Yam JWP, Xu Y, Cui Y. Roles and Molecular Mechanisms of Biomarkers in Hepatocellular Carcinoma with Microvascular Invasion: A Review. J Clin Transl Hepatol 2023; 11:1170-1183. [PMID: 37577231 PMCID: PMC10412705 DOI: 10.14218/jcth.2022.00013s] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2022] [Revised: 01/18/2023] [Accepted: 03/21/2023] [Indexed: 07/03/2023] Open
Abstract
Hepatocellular carcinoma (HCC) being a leading cause of cancer-related death, has high associated mortality and recurrence rates. It has been of great necessity and urgency to find effective HCC diagnosis and treatment measures. Studies have shown that microvascular invasion (MVI) is an independent risk factor for poor prognosis after hepatectomy. The abnormal expression of biomacromolecules such as circ-RNAs, lncRNAs, STIP1, and PD-L1 in HCC patients is strongly correlated with MVI. Deregulation of several markers mentioned in this review affects the proliferation, invasion, metastasis, EMT, and anti-apoptotic processes of HCC cells through multiple complex mechanisms. Therefore, these biomarkers may have an important clinical role and serve as promising interventional targets for HCC. In this review, we provide a comprehensive overview on the functions and regulatory mechanisms of MVI-related biomarkers in HCC.
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Affiliation(s)
- Xudong Zhao
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Yudan Wang
- Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Haoming Xia
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Shuqiang Liu
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Ziyue Huang
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Risheng He
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Liang Yu
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
- Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Nanfeng Meng
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Hang Wang
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Junqi You
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Jinglin Li
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
| | - Judy Wai Ping Yam
- Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Yi Xu
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
- Department of Pathology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
- Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou, China
- Key Laboratory of Functional and Clinical Translational Medicine, Fujian Province University, Xiamen Medical College, Xiamen, Fujian, China
- Jiangsu Province Engineering Research Center of Tumor Targeted Nano Diagnostic and Therapeutic Materials, Yancheng Teachers University, Yancheng, Jiangsu, China
- Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang province, Hangzhou, Zhejiang, China
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China
- State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Genomics, Peking University Shenzhen Graduate School, Shenzhen, Guangdong, China
- Key Laboratory of Intelligent Pharmacy and Individualized Therapy of Huzhou, Department of Pharmacy, Changxing People’s Hospital, Changxing, Zhejiang, China
| | - Yunfu Cui
- Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
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Verma S, Sahu BD, Mugale MN. Role of lncRNAs in hepatocellular carcinoma. Life Sci 2023; 325:121751. [PMID: 37169145 DOI: 10.1016/j.lfs.2023.121751] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 04/21/2023] [Accepted: 04/29/2023] [Indexed: 05/13/2023]
Abstract
Hepatocellular carcinoma (HCC) is among the deadliest cancer in human malignancies. It is the most common and severe type of primary liver cancer. However, the molecular mechanisms underlying HCC pathogenesis remain poorly understood. Long non-coding RNAs (lncRNAs), a new kind of RNA and epigenetic factors, play a crucial role in tumorigenesis and the progression of HCC. LncRNAs are capable of promoting the autophagy, proliferation, and migration of tumor cells by targeting and modulating the expression of downstream genes in signaling pathways related to cancer; these transcripts modify the activity and expression of various tumor suppressors and oncogenes. LncRNAs could act as biomarkers for treatment approaches such as immunotherapy, chemotherapy, and surgery to effectively treat HCC patients. Improved knowledge regarding the aetiology of HCC may result from an advanced understanding of lncRNAs. Enhanced oxidative stress in the mitochondrial and Endoplasmic reticulum leads to the activation of unfolded protein response pathway that plays a crucial role in the pathophysiology of hepatocellular carcinoma. The mutual regulation between LncRNAs and Endoplasmic reticulum (ER) stress in cancer and simultaneous activation of the unfolded protein response (UPR) pathway determines the fate of tumor cells in HCC. Mitochondria-associated lncRNAs work as essential components of several gene regulatory networks; abnormal regulation of mitochondria-associated lncRNAs may lead to oncogenesis, which provides further insight into the understanding of tumorigenesis and therapeutic strategies.
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Affiliation(s)
- Smriti Verma
- Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Bidhya Dhar Sahu
- Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Changsari, 781101, Assam, India
| | - Madhav Nilakanth Mugale
- Division of Toxicology and Experimental Medicine, CSIR-Central Drug Research Institute (CSIR-CDRI), Lucknow 226031, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
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Chen X, Lv Q, Liu Y. A Comprehensive Genome-Wide Analysis of lncRNA Expression Profile during Hepatic Carcinoma Cell Proliferation Promoted by Phospholipase Cγ2. CYTOL GENET+ 2023. [DOI: 10.3103/s0095452723020032] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
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Ectopic expression of lncRNA MVIH as a potential diagnostic biomarker in cervical cancer. Genes Cancer 2022; 13:52-59. [DOI: 10.18632/genesandcancer.224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2022] [Accepted: 11/18/2022] [Indexed: 11/24/2022] Open
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Li J, Quan X, Lei S, Chen G, Hong J, Huang Z, Wang Q, Song W, Yang X. LncRNA MEG3 alleviates PFOS induced placental cell growth inhibition through its derived miR-770 targeting PTX3. ENVIRONMENTAL POLLUTION (BARKING, ESSEX : 1987) 2022; 293:118542. [PMID: 34801623 DOI: 10.1016/j.envpol.2021.118542] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/26/2021] [Revised: 10/14/2021] [Accepted: 11/15/2021] [Indexed: 06/13/2023]
Abstract
Perfluorooctane sulfonic acid (PFOS) is a persistent environmental pollutant. Exposure to PFOS has been associated with abnormal fetal development. The long non-coding RNA (lncRNA) has been showed to play a role in fetal growth restriction (FGR), preeclampsia (PE) and other pregnancy complications. Whether the lncRNA contributes to PFOS-induced toxicity in the placenta remains unknown. In this study, we investigated the function of lncRNA MEG3 and its derived miR-770 in PFOS-induced placental toxicity. Pregnant mice received gavage administration of different concentrations of PFOS (0.5, 2.5, and 12.5 mg/kg/day) from GD0 to GD17, and HTR-8/SVneo cells were treated with PFOS in the concentrations of 0, 10-1, 1, 10 μM. We found that expression levels of miR-770 and its host gene MEG3 were reduced in mice placentas and HTR-8/SVneo cells with exposure of PFOS. A significant hypermethylation was observed at MEG3 promoter in placentas of mice gestational-treated with PFOS. We also confirmed that MEG3 and miR-770 overexpression alleviated the cell growth inhibition induced by PFOS. Furthermore, PTX3 (Pentraxin 3) was identified as the direct target of miR-770 and it was enhanced after PFOS exposure. In summary, our results suggested that MEG3 alleviate PFOS-induced placental cell inhibition through MEG3/miR-770/PTX3 axis.
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Affiliation(s)
- Jing Li
- School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
| | - Xiaojie Quan
- School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China
| | - Saifei Lei
- Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, 15261, USA
| | - Gang Chen
- School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China
| | - Jiawei Hong
- School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China
| | - Zhenyao Huang
- School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China
| | - Qi Wang
- School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China
| | - Weiyi Song
- School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China
| | - Xinxin Yang
- School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China
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Xue H, Gao H, Xia H, Li S, Li N, Gao C, Duan Y, Ren Y, Zhang H, Liu J, Gao W. IncRNA MVIH correlates with disease features, predicts treatment response and survival in pediatric acute myeloid leukemia. J Clin Lab Anal 2021; 35:e23739. [PMID: 33704838 PMCID: PMC8059728 DOI: 10.1002/jcla.23739] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Revised: 02/02/2021] [Accepted: 02/09/2021] [Indexed: 11/06/2022] Open
Abstract
OBJECTIVE Long non-coding RNA microvascular invasion in hepatocellular carcinoma (lnc-MVIH) is correlated with unfavorable prognosis in several malignancies, while limitedly studied in pediatric acute myeloid leukemia (AML). This study aimed to investigate the correlation of lnc-MVIH with disease features, response to induction therapy, and survival in pediatric AML patients. METHODS A total of 129 de novo pediatric AML patients who were retrospectively analyzed and 60 children with non-malignant hematological diseases who underwent bone marrow examination were reviewed as controls. Bone marrow mononuclear cells (BMMCs) were isolated from all participants to detect lnc-MVIH expression by reverse transcription-quantitative polymerase chain reaction. The complete remission status after 1 course of induction therapy, event-free survival, and overall survival of pediatric AML patients were recorded. RESULTS Lnc-MVIH was upregulated in pediatric AML patients compared with controls (p < 0.001). In pediatric AML patients, lnc-MVIH was correlated with increased bone marrow blasts, less inv(16) or t(16;16) abnormity, and higher Chinese Medical Association (CMA) risk stratification (all p < 0.05), whereas its correlation with National Comprehensive Cancer Network (NCCN) risk stratification was not statistically significant (p = 0.098). As for prognosis, lnc-MVIH high expression patients presented with lower complete response rate to 1 course of induction therapy (61.5% vs. 79.7%, p = 0.024), shorter event-free survival (median 12.0 months vs. 22.0 months, p = 0.006), and overall survival (median 28.0 months vs. 42.0 months, p = 0.043) compared with lnc-MVIH low expression patients. CONCLUSION Lnc-MVIH correlates with poor treatment response and unfavorable survival in pediatric AML.
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Affiliation(s)
- Hongjuan Xue
- Department of Pediatric Hematology and OncologyXingtai People's HospitalXingtaiChina
| | - Haili Gao
- Department of Pediatric Hematology and OncologyThe Children's Hospital Affiliated of Zhengzhou UniversityZhengzhouChina
| | - Hong Xia
- Department of PediatricXingtai People's HospitalXingtaiChina
| | - Shaofei Li
- Department of Digestive EndoscopyMinmetals Hanxing General HospitalHandanChina
| | - Na Li
- Department of Pediatric Hematology and OncologyXingtai People's HospitalXingtaiChina
| | - Chao Gao
- Department of Pediatric Hematology and OncologyXingtai People's HospitalXingtaiChina
| | - Yuwen Duan
- Department of Pediatric Hematology and OncologyXingtai People's HospitalXingtaiChina
| | - Yanfei Ren
- Department of Pediatric Hematology and OncologyXingtai People's HospitalXingtaiChina
| | - Henglu Zhang
- Department of Pediatric Hematology and OncologyXingtai People's HospitalXingtaiChina
| | - Jingzheng Liu
- Department of Pediatric Hematology and OncologyThe Central Hospital of Enshi Tujia and Miao Autonomous PrefectureEnshiChina
| | - Wei Gao
- Department of Pediatric Hematology and OncologyXingtai People's HospitalXingtaiChina
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Cardoso AM, Morais CM, Rebelo O, Tão H, Barbosa M, Pedroso de Lima MC, Jurado AS. Downregulation of long non-protein coding RNA MVIH impairs glioblastoma cell proliferation and invasion through an miR-302a-dependent mechanism. Hum Mol Genet 2021; 30:46-64. [PMID: 33438023 DOI: 10.1093/hmg/ddab009] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Revised: 12/18/2020] [Accepted: 01/05/2021] [Indexed: 02/07/2023] Open
Abstract
Glioblastoma (GB) is the most frequent and malignant type of brain tumor, for which no effective therapy exists. The high proliferative and invasive nature of GB, as well as its acquired resistance to chemotherapy, makes this type of cancer extremely lethal shortly after diagnosis. Long non-protein coding RNAs (lncRNA) are a class of regulatory RNAs whose levels can be dysregulated in the context of diseases, unbalancing several physiological processes. The lncRNA associated with microvascular invasion in hepatocellular carcinoma (lncRNA-MVIH), overexpressed in several cancers, was described to co-precipitate with phosphoglycerate kinase 1 (PGK1), preventing secretion of this enzyme to the extracellular environment and promoting cell migration and invasion. We hypothesized that, by silencing the expression of lncRNA-MVIH, the secretion of PGK1 would increase, reducing GB cell migration and invasion capabilities. We observed that lncRNA-MVIH silencing in human GB cells significantly decreased glycolysis, cell growth, migration, and invasion and sensitized GB cells to cediranib. However, no increase in extracellular PGK1 was observed as a consequence of lncRNA-MVIH silencing, and therefore, we investigated the possibility of a mechanism of miRNA sponge of lncRNA-MVIH being in place. We found that the levels of miR-302a loaded onto RISC increased in GB cells after lncRNA-MVIH silencing, with the consequent downregulation of several miR-302a molecular targets. Our findings suggest a new mechanism of action of lncRNA-MVIH as a sponge of miR-302a. We suggest that lncRNA-MVIH knockdown may be a promising strategy to address GB invasiveness and chemoresistance, holding potential towards its future application in a clinical context.
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Affiliation(s)
- Ana M Cardoso
- CNC - Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, IIIUC - Institute for Interdisciplinary Research, Coimbra, Portugal
| | - Catarina M Morais
- Department of Life Sciences, University of Coimbra, Calçada Martim de Freitas, 3000-456 Coimbra, Portugal
| | - Olinda Rebelo
- Neuropathology Laboratory, Neurology Service, University Hospital of Coimbra, 3004-561 Coimbra, Portugal
| | - Hermínio Tão
- Neurosurgery Service, University Hospital of Coimbra, 33004-561 Coimbra, Portugal
| | - Marcos Barbosa
- Neurosurgery Service, University Hospital of Coimbra, 33004-561 Coimbra, Portugal.,Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal
| | - Maria C Pedroso de Lima
- CNC - Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, IIIUC - Institute for Interdisciplinary Research, Coimbra, Portugal
| | - Amália S Jurado
- CNC - Center for Neuroscience and Cell Biology, CIBB - Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, IIIUC - Institute for Interdisciplinary Research, Coimbra, Portugal.,Department of Life Sciences, University of Coimbra, Calçada Martim de Freitas, 3000-456 Coimbra, Portugal
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Li J, Quan XJ, Chen G, Hong JW, Wang Q, Xu LL, Wang BH, Yu ZH, Yu HM. PFOS-induced placental cell growth inhibition is partially mediated by lncRNA H19 through interacting with miR-19a and miR-19b. CHEMOSPHERE 2020; 261:127640. [PMID: 32738709 DOI: 10.1016/j.chemosphere.2020.127640] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Revised: 07/01/2020] [Accepted: 07/05/2020] [Indexed: 05/15/2023]
Abstract
Perfluorooctane sulfonic acid (PFOS), a persistent environmental pollutant, has been associated with decreased birth weight. The dysregulation of long non-coding RNA (lncRNA) H19 has been implicated in pregnancy complications such as intra-uterine growth retardation (IUGR), preeclampsia (PE), however, the expression and function of H19 in PFOS-exerted detrimental effects in the placenta remains to be unveiled. Here, we explored the role of H19 in PFOS-induced placental toxicity. Results showed that PFOS caused decreased cell growth in human HTR-8/SVneo cells. Expression of H19 was increased, while miR-19a and miR-19b expression were decreased in mice placenta tissues and in HTR-8/SVneo cells exposed to PFOS. A significant hypomethylation was observed at the H19 promoter in the placentas of mice that were gestational exposed to high dose of PFOS. H19 was confirmed to bind with miR-19a and miR-19b, targeting SMAD4. Furthermore, H19 appeared to partially improve the cell growth of HTR-8/SVneo cells exposed to PFOS via upregulation of miR-19a and miR-19b. In summary, our findings revealed that H19/miR-19a and miR-19b/SMAD4 axis exerted important functions in PFOS-induced placenta cell toxicity.
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Affiliation(s)
- Jing Li
- School of Public Health, Xuzhou Medical College, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
| | - Xiao-Jie Quan
- School of Public Health, Xuzhou Medical College, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
| | - Gang Chen
- School of Public Health, Xuzhou Medical College, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
| | - Jia-Wei Hong
- School of Public Health, Xuzhou Medical College, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
| | - Qi Wang
- School of Public Health, Xuzhou Medical College, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
| | - Lin-Lin Xu
- School of Public Health, Xuzhou Medical College, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
| | - Bing-Hua Wang
- School of Public Health, Xuzhou Medical College, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
| | - Ze-Hua Yu
- School of Public Health, Xuzhou Medical College, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
| | - Hong-Min Yu
- School of Public Health, Xuzhou Medical College, 209 Tong-Shan Road, Xuzhou, Jiangsu, 221002, China.
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13
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Hu S, Zheng Q, Xiong J, Wu H, Wang W, Zhou W. Long non-coding RNA MVIH promotes cell proliferation, migration, invasion through regulating multiple cancer-related pathways, and correlates with worse prognosis in pancreatic ductal adenocarcinomas. Am J Transl Res 2020; 12:2118-2135. [PMID: 32509206 PMCID: PMC7270031] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2019] [Accepted: 04/24/2020] [Indexed: 06/11/2023]
Abstract
We aimed to explore the effect of long non-coding RNA MVIH (lnc-MVIH) on cell proliferation, migration as well as invasion, and investigate the landscape of its molecular mechanism in pancreatic ductal adenocarcinomas (PDAC). Control overexpression (OE-NC group) and lnc-MVIH overexpression (OE-MVIH group) plasmids were transfected in BxPC-3 cells; control knock-down (KD-NC group) and lnc-MVIH knock-down (KD-MVIH group) plasmids were transfected in PANC-1 cells. Cellular functions were measured and mRNA sequencing was conducted. In 70 PDAC patients, lnc-MVIH expression in tumor and adjacent tissues was detected. Lnc-MVIH expression was higher in human PDAC cell lines than human normal pancreatic ductal epithelial cell line. Cell proliferation, migration and invasion were increased in OE-MVIH group compared to OE-NC group, but decreased in KD-MVIH group compared to KD-NC group. mRNA sequencing showed 145 differentially expressing genes (DEGs) upregulated in OE-MVIH group vs. OE-NC group and downregulated in KD-MVIH group vs. KD-NC group, and 51 DEGs downregulated in OE-MVIH group vs. OE-NC group and upregulated in KD-MVIH group vs. KD-NC group. These DEGs were enriched in several cancer-related pathways (including Hippo signaling pathway, cell cycle, Forkhead box O signaling pathway, apoptosis and advanced glycation end products-RAGE signaling pathway), and the effect of lnc-MVIH on regulating these DEGs was further validated by RT-qPCR. In PDAC patients, lnc-MVIH expression was increased in tumor tissue and correlated with advanced tumor size, lymph node metastasis, TNM stage and poor OS. In conclusion, lnc-MVIH might be a potential therapeutic target which regulated multiple cancer-related pathways in PDAC.
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Affiliation(s)
- Shaobo Hu
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, China
| | - Qichang Zheng
- Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, China
| | - Jiongxin Xiong
- Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, China
| | - Heshui Wu
- Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, China
| | - Weici Wang
- Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, China
| | - Wei Zhou
- Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhan, China
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Wang Q, Ye B, Wang P, Yao F, Zhang C, Yu G. Overview of microRNA-199a Regulation in Cancer. Cancer Manag Res 2019; 11:10327-10335. [PMID: 31849522 PMCID: PMC6911337 DOI: 10.2147/cmar.s231971] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2019] [Accepted: 11/23/2019] [Indexed: 12/17/2022] Open
Abstract
microRNAs (miRNAs) are a class of endogenous short, non-coding RNAs that regulate a multitude of genes at the post-transcriptional level. miR-199, which is a highly conserved miRNA family, consists of miR-199a and miR-199b. Researchers mainly focused on miR-199a over the past few years. Functional studies have demonstrated that mature miR-199a is a key player in the maintenance of normal homeostasis and in the regulation of disease pathogenesis. Here, we summarize the biological functions of miR-199a and review recent research on its roles in the physiological processes of cancer cells, such as proliferation, migration, invasion, apoptosis, autophagy and glycometabolism.
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Affiliation(s)
- Qiwen Wang
- Henan International Joint Laboratory of Pulmonary Fibrosis, College of Life Science, Henan Normal University, Xinxiang 453007, Henan, People's Republic of China.,State Key Laboratory Cell Differentiation and Regulation, College of Life Science, Henan Normal University, Xinxiang 453007, People's Republic of China
| | - Bingyu Ye
- Henan International Joint Laboratory of Pulmonary Fibrosis, College of Life Science, Henan Normal University, Xinxiang 453007, Henan, People's Republic of China.,State Key Laboratory Cell Differentiation and Regulation, College of Life Science, Henan Normal University, Xinxiang 453007, People's Republic of China
| | - Ping Wang
- Henan International Joint Laboratory of Pulmonary Fibrosis, College of Life Science, Henan Normal University, Xinxiang 453007, Henan, People's Republic of China.,State Key Laboratory Cell Differentiation and Regulation, College of Life Science, Henan Normal University, Xinxiang 453007, People's Republic of China
| | - Fenjie Yao
- Henan International Joint Laboratory of Pulmonary Fibrosis, College of Life Science, Henan Normal University, Xinxiang 453007, Henan, People's Republic of China.,State Key Laboratory Cell Differentiation and Regulation, College of Life Science, Henan Normal University, Xinxiang 453007, People's Republic of China
| | - Chunyan Zhang
- Henan International Joint Laboratory of Pulmonary Fibrosis, College of Life Science, Henan Normal University, Xinxiang 453007, Henan, People's Republic of China.,State Key Laboratory Cell Differentiation and Regulation, College of Life Science, Henan Normal University, Xinxiang 453007, People's Republic of China
| | - Guoying Yu
- Henan International Joint Laboratory of Pulmonary Fibrosis, College of Life Science, Henan Normal University, Xinxiang 453007, Henan, People's Republic of China.,State Key Laboratory Cell Differentiation and Regulation, College of Life Science, Henan Normal University, Xinxiang 453007, People's Republic of China
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15
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Jiang Z, Yu Q, Luo X. Identification of long non-coding RNA MVIH as a prognostic marker and therapeutic target in acute myeloid leukemia. J Clin Lab Anal 2019; 34:e23113. [PMID: 31724217 PMCID: PMC7171335 DOI: 10.1002/jcla.23113] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Revised: 10/17/2019] [Accepted: 10/17/2019] [Indexed: 11/22/2022] Open
Abstract
Background This study aimed to investigate the correlation of long non‐coding RNA microvascular invasion in hepatocellular carcinoma (lncRNA MVIH) with disease risk, disease conditions, and prognosis of acute myeloid leukemia (AML), and also to investigate the influence of lncRNA MVIH on AML cell activities in vitro. Methods A total of 212 AML patients and 70 controls were consecutively recruited. Their bone marrow mononuclear cells (BMMCs) were isolated, and lncRNA MVIH was detected by reverse transcription quantitative‐polymerase chain reaction. In AML patients, complete remission (CR), event‐free survival (EFS), and overall survival (OS) were assessed. In vitro, lncRNA MVIH expression in AML cell lines was determined, and the effect of lncRNA MVIH on AML cell proliferation and apoptosis was assessed. Results LncRNA MVIH expression was increased in AML patients compared to controls, and receiver operating characteristic curve showed that lncRNA MVIH predicted elevated AML risk (area under curve: 0.742 [95% CI: 0.674‐0.810]). In AML patients, no correlation of lncRNA MVIH expression with French‐American‐British classification was observed, while lncRNA MVIH high expression correlated with worse risk stratification. Moreover, lncRNA MVIH expression negatively correlated with CR achievement, EFS and OS. In vitro, lncRNA MVIH was overexpressed in AML cell lines (KG‐1, ME‐1, and HT‐93) compared to normal BMMCs. Furthermore, lncRNA MVIH downregulation reduced KG‐1 cell proliferation but increased apoptosis, whereas lncRNA MVIH upregulation raised HL‐60 cell proliferation but decreased apoptosis. Conclusion LncRNA MVIH may not only serve as a prognostic marker but also act as a therapeutic target in AML.
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Affiliation(s)
- Zhiyong Jiang
- Department of Hematology, Jinhua People's Hospital, Zhejiang, China
| | - Qinghong Yu
- Department of Hematology, The First Affiliated Hospital, Zhejiang University, Hangzhou, China
| | - Xinguo Luo
- Department of Hematology, Jinhua People's Hospital, Zhejiang, China
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16
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Ke S, Zhou X. LncRNA MVIH knockdown inhibits the malignancy progression through downregulating miR-505 mediated HMGB1 and CCNE2 in acute myeloid leukemia. Transl Cancer Res 2019; 8:2526-2534. [PMID: 35117009 PMCID: PMC8799070 DOI: 10.21037/tcr.2019.10.12] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2019] [Accepted: 09/12/2019] [Indexed: 11/07/2022]
Abstract
Background This study aimed to investigate the regulatory role of long non-coding RNA associated with microvascular invasion in hepatocellular carcinoma (lnc-MVIH) in the progression of acute myeloid leukemia (AML) and the underlying mechanism. Methods Lnc-MVIH expression was detected in AML cell lines AML-193, KG-1, HL-60, OCI-AML2 and primary normal bone marrow mononuclear cells (BMMC). The effect of lnc-MVIH knockdown on cell proliferation, apoptosis and miR-505 expression were detected by transfection of lnc-MVIH shRNA and control shRNA into KG-1 cells. And the effect of miR-505 knockdown on lnc-MVIH, cell proliferation, cell apoptosis as well as potential miR-505 target genes [high mobility group box 1 (HMGB1) and cyclin E2 (CCNE2)] in lnc-MVIH knockdown treated KG-1 cells was assessed by transfection of lnc-MVIH shRNA and lnc-MVIH shRNA & miR-505 shRNA into KG-1 cells. Results Lnc-MVIH expression was elevated in AML-193, KG-1, OCI-AML2 cell lines, but similar in HL-60 cell line compared with primary normal BMMC. Lnc-MVIH knockdown inhibited cell proliferation but promoted cell apoptosis in KG-1 cells, meanwhile miR-505 expression was increased by lnc-MVIH knockdown in KG-1 cells. And in rescue experiments, miR-505 knockdown had no effect on expression of lnc-MVIH, while it increased the expressions of HMGB1 and CCNE2, promoted cell proliferation, inhibited cell apoptosis in lnc-MVIH knockdown treated KG-1 cells. Conclusions Lnc-MVIH knockdown inhibits cell proliferation but promotes cell apoptosis via regulating miR-505 mediated HMGB1 and CCNE2 in AML.
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Affiliation(s)
- Shandong Ke
- Department of Hematology, Huangshi Central Hospital, Huangshi 435000, China
| | - Xiaofen Zhou
- Department of Hematology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang 441021, China
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17
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Zhao J, Xie Y. Progress in research of hepatocellular carcinoma with tumor thrombus. Shijie Huaren Xiaohua Zazhi 2019; 27:1239-1247. [DOI: 10.11569/wcjd.v27.i20.1239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) with tumor thrombus is a hot and difficult issue in the study of HCC, and many key issues concerning this condition are still controversial. Clinical guidelines and treatment recommendations vary widely between the East and the West, and efficacy remains unsatisfactory. In recent years, with the progress of comprehensive tumor treatment concept and the rapid development of surgical techniques, perioperative management, interventional therapy, radiotherapy, targeted therapy, and other treatment methods, the overall survival rate of HCC with tumor thrombus has been significantly extended and encouraging efficacy has been achieved. However, the core issues on how to select individualized treatment to achieve optimal treatment and how to prevent postoperative recurrence still need to be studied and discussed. This article reviews the progress in the research of hepatic carcinoma with portal vein thrombus, inferior vena cava thrombus, or bile duct thrombus.
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Affiliation(s)
- Jian Zhao
- Department of Hepatobiliary Surgery, Rocket Army Featured Medical Center, Beijing 100088, China
| | - Yu Xie
- Department of Hepatobiliary Surgery, Rocket Army Featured Medical Center, Beijing 100088, China
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18
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Song SK, Park MG, Park SK, Chung CW, Park Y. MicroRNAs associated with microvascular invasion in hepatocellular carcinoma and their prognostic impacts in patients undergoing hepatic resection. Oncol Lett 2019; 18:6293-6303. [PMID: 31788107 DOI: 10.3892/ol.2019.10987] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2019] [Accepted: 08/30/2019] [Indexed: 12/12/2022] Open
Abstract
Although microvascular invasion (McVI) has prognostic value for patients with hepatocellular carcinoma (HCC) who have undergone hepatic resection, few studies have investigated the relationship between McVI and the aberrant expression of microRNAs (miRNAs). The present study identified the miRNAs that were selectively expressed in HCC with McVI and investigated their prognostic value. Clinical data and the miRNA expression profiles of 372 patients with HCC were extracted from The Cancer Genome Atlas database. miRNAs that were differentially expressed between patients with McVI and those without vascular invasion (VI) were identified and investigated as potential prognostic factors for HCC. The results demonstrated that McVI was a significant predictor of shortened recurrence-free survival (RFS). The 3 year RFS rate in patients with HCC accompanied by McVI was 28.2 and 49.3% in HCC without VI (P<0.001). miRNA-141/-582/-9 were upregulated, while miRNA-675 was downregulated in patients with McVI when compared with HCC patients without VI. Log2 fold-changes of miRNA-141/-582/-675/-9 were 0.80 [false discovery rate (FDR), 0.005], 0.55 (FDR, 0.045), -0.99 (FDR, 0.005) and 1.22 (FDR, <0.001), respectively. Kaplan-Meier analysis indicated that the overexpression of miR-141/-582/-9 was significantly associated with poor RFS and a poor overall survival. A text mining analysis revealed that these miRNAs were significantly associated with multifaceted hallmarks of cancer, including 'invasion and metastasis'. In conclusion, the overexpression of miRNA-141/-582/-9 was associated with McVI and a poor survival in patients undergoing hepatic resection for HCC.
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Affiliation(s)
- Sung Kyu Song
- Department of Surgery, Catholic Kwandong University International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon 22711, Republic of Korea
| | - Min Geun Park
- Department of Surgery, Catholic Kwandong University International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon 22711, Republic of Korea
| | - Seung-Keun Park
- Department of Supercomputing M&S Technology Development, Korea Institute of Science and Technology Information, Daejeon 34141, Republic of Korea
| | - Chul-Woon Chung
- Department of Surgery, Catholic Kwandong University International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon 22711, Republic of Korea
| | - Yongkeun Park
- Department of Surgery, Catholic Kwandong University International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon 22711, Republic of Korea
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Shang W, Adzika GK, Li Y, Huang Q, Ding N, Chinembiri B, Rashid MSI, Machuki JO. Molecular mechanisms of circular RNAs, transforming growth factor-β, and long noncoding RNAs in hepatocellular carcinoma. Cancer Med 2019; 8:6684-6699. [PMID: 31523930 PMCID: PMC6826001 DOI: 10.1002/cam4.2553] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2019] [Revised: 08/23/2019] [Accepted: 08/26/2019] [Indexed: 12/17/2022] Open
Abstract
At the heart of hepatocellular carcinoma (HCC) lies disruption of signaling pathways at the level of molecules, genes, and cells. Non‐coding RNAs (ncRNAs) have been implicated in the disease progression of HCC. For instance, dysregulated expression of circular RNAs (circRNAs) has been observed in patients with HCC. As such, these RNAs are potential therapeutic targets and diagnostic markers for HCC. Long non‐coding RNAs (lncRNAs), a type of ncRNA, have also been recognized to participate in the initiation and progression of HCC. Transforming growth factor‐beta (TGF‐β) is another element which is now recognized to play crucial roles in HCC. It has been implicated in many biological processes such as survival, immune surveillance, and cell proliferation. In HCC, TGF‐β promotes disease progression by two mechanisms: an intrinsic signaling pathway and the extrinsic pathway. Through these pathways, it modulates various microenvironment factors such as inflammatory mediators and fibroblasts. An interesting yet‐to‐be resolved concept is whether the HCC‐promoting role of TGF‐β pathways is limited to a subset of HCC patients or it is involved in the whole process of HCC development. This review summarizes recent advancements to highlight the roles of circRNAs, lncRNAs, and TGF‐β in HCC.
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Affiliation(s)
- Wenkang Shang
- Department of Laboratory Medicine, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | | | - Yujie Li
- Department of Clinical Laboratory, The First People's Hospital of Kunshan, Kunshan, Jiangsu, China
| | - Qike Huang
- The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China
| | - Ningding Ding
- Department of Neurophysiology and Location Diagnosis, Guangdong 39 Brain Hospital, Guangzhou, Guangdong, China
| | - Bianca Chinembiri
- Physiology Department, Xuzhou Medical University, Xuzhou, Jiangsu, China
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20
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Zhang Y, Lin S, Yang X, Zhang X. Prognostic and Clinicopathological Significance of lncRNA MVIH in Cancer Patients. J Cancer 2019; 10:1503-1510. [PMID: 31031860 PMCID: PMC6485214 DOI: 10.7150/jca.28541] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2018] [Accepted: 10/24/2018] [Indexed: 01/25/2023] Open
Abstract
Objectives: LncRNA associated with microvascular invasion in hepatocellular carcinoma (lncRNA MVIH) is a newly discovered long non-coding RNA that aberrantly up-regulates and holds prognostic value in various tumors. The aim of the review and meta-analysis is to assess its prognostic potential and functions in malignant tumors. Materials and methods: PubMed, PMC, EMBASE, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang Database were carefully searched for articles published as of Jan. 1, 2018. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to demonstrate prognostic value of lncRNA MVIH using Stata 12.0 software. Results: Six original studies including 830 cancer patients were ultimately enrolled in this meta-analysis. The pooled results showed that elevated lncRNA MVIH expression was significantly correlated with unfavorable OS (HR=2.17, 95% CI: 1.58-2.76, p < 0.001) and RFS/DFS/PFS (HR=2.21, 95% CI: 1.54-2.87, p < 0.001) in cancer patients. Additionally, high expression of lncRNA MVIH was related to positive lymph node metastasis (OR = 3.04, 95% CI: 1.37-6.75, p = 0.006) and advanced clinical stage (OR = 2.52, 95% CI: 1.68-3.79, p < 0.001). Conclusions: LncRNA MVIH over-expression was associated with poor clinical outcomes in multiple cancer types. More studies are warranted to verify and strengthen the clinical value of lncRNA MVIH in human cancers.
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Affiliation(s)
- Yi Zhang
- Department of General Surgery, the First People's Hospital of Neijiang, Neijiang 641000, Sichuan Province, P. R. China
| | - Shibu Lin
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Hainan, Medical College, Haikou 570102, Hainan Province, P. R. China
| | - Xianjin Yang
- Department of General Surgery, the First People's Hospital of Neijiang, Neijiang 641000, Sichuan Province, P. R. China
| | - Xu Zhang
- Department of General Surgery, the First People's Hospital of Neijiang, Neijiang 641000, Sichuan Province, P. R. China
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21
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Abbastabar M, Sarfi M, Golestani A, Khalili E. lncRNA involvement in hepatocellular carcinoma metastasis and prognosis. EXCLI JOURNAL 2018; 17:900-913. [PMID: 30564069 PMCID: PMC6295623 DOI: 10.17179/excli2018-1541] [Citation(s) in RCA: 70] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Accepted: 08/20/2018] [Indexed: 12/15/2022]
Abstract
Eukaryotic lncRNAs are RNA molecules defined to be greater than 200 bp in length that are not translated to a protein and operate through several mechanisms, including participating in chromatin remodeling and methylation, influencing the integrity and stability of proteins and complexes, or acting as a sponge for miRNA inhibition. A number of recent studies have concentrated on the relationship between long non-coding RNAs (lncRNAs) and cancer. Hepatocellular carcinoma (HCC) is the most prevalent histological type of liver tumors, accounting for about 80 % of the cases worldwide. Lack of proper molecular markers for diagnosis of HCC and treatment evaluation is a significant problem. Dysregulated expression of HCC-related lncRNAs such as MEG-3, MALAT1, HULC, HOTAIR, and H19 have been identified and closely related with tumorigenesis, metastasis, prognosis and diagnosis. In this review, we summarized recent highlighted functions and molecular mechanisms of the most extensively studied lncRNAs in the pathophysiology of hepatocellular carcinoma and their potential for serving as probable therapeutic targets.
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Affiliation(s)
- Maryam Abbastabar
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, I.R. Iran
| | - Mohammad Sarfi
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, I.R. Iran
| | - Abolfazl Golestani
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, I.R. Iran
| | - Ehsan Khalili
- Department of Clinical Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, I.R. Iran
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Hu X, Jiang J, Xu Q, Ni C, Yang L, Huang D. A Systematic Review of Long Noncoding RNAs in Hepatocellular Carcinoma: Molecular Mechanism and Clinical Implications. BIOMED RESEARCH INTERNATIONAL 2018; 2018:8126208. [PMID: 30105249 PMCID: PMC6076971 DOI: 10.1155/2018/8126208] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Accepted: 04/10/2018] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC) has the second highest mortality rate worldwide among all cancers. Previous studies have revealed the significant involvement of long noncoding RNAs (lncRNAs) in numerous human cancers including HCC. Both oncogenic and tumor repressive lncRNAs have been identified and implicated in the complex process of hepatocarcinogenesis. They can be further explored as prospective diagnostic, prognostic, and therapeutic markers for HCC. An in-depth understanding of lncRNAs' mechanism in HCC is therefore required to fully explore their potential role. In the current review, we will concentrate on the underlying function, molecular mechanisms, and potential clinical implications of lncRNA in HCC.
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Affiliation(s)
- Xiaoge Hu
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
- Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
| | - Jiahong Jiang
- Department of Second Clinical Medical College, Zhejiang Chinese Medicine University, Hangzhou, Zhejiang 310053, China
| | - Qiuran Xu
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
- Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
| | - Chao Ni
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
- Department of General Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
| | - Liu Yang
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
- Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
| | - Dongsheng Huang
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
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El Khodiry A, Afify M, El Tayebi HM. Behind the curtain of non-coding RNAs; long non-coding RNAs regulating hepatocarcinogenesis. World J Gastroenterol 2018; 24:549-572. [PMID: 29434445 PMCID: PMC5799857 DOI: 10.3748/wjg.v24.i5.549] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2017] [Revised: 01/17/2018] [Accepted: 01/23/2018] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common and aggressive cancers worldwide. HCC is the fifth common malignancy in the world and the second leading cause of cancer death in Asia. Long non-coding RNAs (lncRNAs) are RNAs with a length greater than 200 nucleotides that do not encode proteins. lncRNAs can regulate gene expression and protein synthesis in several ways by interacting with DNA, RNA and proteins in a sequence specific manner. They could regulate cellular and developmental processes through either gene inhibition or gene activation. Many studies have shown that dysregulation of lncRNAs is related to many human diseases such as cardiovascular diseases, genetic disorders, neurological diseases, immune mediated disorders and cancers. However, the study of lncRNAs is challenging as they are poorly conserved between species, their expression levels aren't as high as that of mRNAs and have great interpatient variations. The study of lncRNAs expression in cancers have been a breakthrough as it unveils potential biomarkers and drug targets for cancer therapy and helps understand the mechanism of pathogenesis. This review discusses many long non-coding RNAs and their contribution in HCC, their role in development, metastasis, and prognosis of HCC and how to regulate and target these lncRNAs as a therapeutic tool in HCC treatment in the future.
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Affiliation(s)
- Aya El Khodiry
- Genetic Pharmacology Research Group, Clinical Pharmacy Unit, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt
| | - Menna Afify
- Genetic Pharmacology Research Group, Clinical Pharmacy Unit, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt
| | - Hend M El Tayebi
- Genetic Pharmacology Research Group, Clinical Pharmacy Unit, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt
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24
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25
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Qiu L, Wang T, Xu X, Wu Y, Tang Q, Chen K. Long Non-Coding RNAs in Hepatitis B Virus-Related Hepatocellular Carcinoma: Regulation, Functions, and Underlying Mechanisms. Int J Mol Sci 2017; 18:ijms18122505. [PMID: 29168767 PMCID: PMC5751108 DOI: 10.3390/ijms18122505] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2017] [Revised: 11/13/2017] [Accepted: 11/20/2017] [Indexed: 12/19/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer death in the world. Hepatitis B virus (HBV) and its X gene-encoded protein (HBx) play important roles in the progression of HCC. Although long non-coding RNAs (lncRNAs) cannot encode proteins, growing evidence indicates that they play essential roles in HCC progression, and contribute to cell proliferation, invasion and metastasis, autophagy, and apoptosis by targeting a large number of pivotal protein-coding genes, miRNAs, and signaling pathways. In this review, we briefly outline recent findings of differentially expressed lncRNAs in HBV-related HCC, with particular focus on several key lncRNAs, and discuss their regulation by HBV/HBx, their functions, and their underlying molecular mechanisms in the progression of HCC.
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Affiliation(s)
- Lipeng Qiu
- Institute of Life Sciences, Jiangsu University, Zhenjiang 212013, China.
| | - Tao Wang
- Institute of Life Sciences, Jiangsu University, Zhenjiang 212013, China.
| | - Xiuquan Xu
- School of Pharmacy, Jiangsu University, Zhenjiang 212013, China.
| | - Yihang Wu
- Department of Pharmacy, College of Life Sciences, China Jiliang University, Hangzhou 310018, China.
| | - Qi Tang
- Institute of Life Sciences, Jiangsu University, Zhenjiang 212013, China.
| | - Keping Chen
- Institute of Life Sciences, Jiangsu University, Zhenjiang 212013, China.
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Drak Alsibai K, Meseure D. Tumor microenvironment and noncoding RNAs as co-drivers of epithelial-mesenchymal transition and cancer metastasis. Dev Dyn 2017; 247:405-431. [PMID: 28691356 DOI: 10.1002/dvdy.24548] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2017] [Revised: 05/31/2017] [Accepted: 06/29/2017] [Indexed: 12/13/2022] Open
Abstract
Reciprocal interactions between cancer cells and tumor microenvironment (TME) are crucial events in tumor progression and metastasis. Pervasive stromal reprogramming of TME modifies numerous cellular functions, including extracellular matrix (ECM) stiffness, inflammation, and immunity. These environmental factors allow selection of more aggressive cells that develop adaptive strategies associating plasticity and epithelial-mesenchymal transition (EMT), stem-like phenotype, invasion, immunosuppression, and resistance to therapies. EMT is a morphomolecular process that endows epithelial tumor cells with mesenchymal properties, including reduced adhesion and increased motility. Numerous studies have demonstrated involvement of noncoding RNAs (ncRNAs), such as miRNAs and lncRNAs, in tumor initiation, progression, and metastasis. NcRNAs regulate every hallmark of cancer and have now emerged as new players in induction and regulation of EMT. The reciprocal regulatory interactions between ncRNAs, TME components, and cancer cells increase the complexity of gene expression and protein translation in cancer. Thus, deeper understanding of molecular mechanisms controlling EMT will not only shed light on metastatic processes of cancer cells, but enhance development of new therapies targeting metastasis. In this review, we will provide recent findings on the role of known ncRNAs relevant to EMT and cancer metastasis and discuss the role of the interaction between ncRNAs and TME as co-drivers of EMT. Developmental Dynamics 247:405-431, 2018. © 2017 Wiley Periodicals, Inc.
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Affiliation(s)
| | - Didier Meseure
- Platform of Investigative Pathology, Curie Institute, Paris, France.,Department of Pathology, Curie Institute, Paris, France
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27
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Boyle M, Mann J. WITHDRAWN: Epigenetics in Chronic Liver Disease. J Hepatol 2017:S0168-8278(17)32255-9. [PMID: 28855099 DOI: 10.1016/j.jhep.2017.08.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2017] [Revised: 08/17/2017] [Accepted: 08/18/2017] [Indexed: 12/04/2022]
Abstract
This article has been withdrawn at the request of the editors. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
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Affiliation(s)
- Marie Boyle
- Institute of Cellular Medicine, Faculty of Medical Sciences, 4(th) Floor, William Leech Building, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK
| | - Jelena Mann
- Institute of Cellular Medicine, Faculty of Medical Sciences, 4(th) Floor, William Leech Building, Newcastle University, Framlington Place, Newcastle upon Tyne, NE2 4HH, UK.
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28
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Niu ZS, Niu XJ, Wang WH. Long non-coding RNAs in hepatocellular carcinoma: Potential roles and clinical implications. World J Gastroenterol 2017; 23:5860-5874. [PMID: 28932078 PMCID: PMC5583571 DOI: 10.3748/wjg.v23.i32.5860] [Citation(s) in RCA: 49] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2017] [Revised: 05/10/2017] [Accepted: 07/22/2017] [Indexed: 02/06/2023] Open
Abstract
Long non-coding RNAs (lncRNAs) are a subgroup of non-coding RNA transcripts greater than 200 nucleotides in length with little or no protein-coding potential. Emerging evidence indicates that lncRNAs may play important regulatory roles in the pathogenesis and progression of human cancers, including hepatocellular carcinoma (HCC). Certain lncRNAs may be used as diagnostic or prognostic markers for HCC, a serious malignancy with increasing morbidity and high mortality rates worldwide. Therefore, elucidating the functional roles of lncRNAs in tumors can contribute to a better understanding of the molecular mechanisms of HCC and may help in developing novel therapeutic targets. In this review, we summarize the recent progress regarding the functional roles of lncRNAs in HCC and explore their clinical implications as diagnostic or prognostic biomarkers and molecular therapeutic targets for HCC.
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MESH Headings
- Antineoplastic Agents/therapeutic use
- Biomarkers, Tumor/analysis
- Biomarkers, Tumor/antagonists & inhibitors
- Biomarkers, Tumor/genetics
- Biomarkers, Tumor/metabolism
- Carcinogenesis/genetics
- Carcinoma, Hepatocellular/diagnosis
- Carcinoma, Hepatocellular/drug therapy
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/mortality
- Disease Progression
- Early Detection of Cancer/methods
- Epigenesis, Genetic
- Gene Expression Regulation, Neoplastic
- Humans
- Liver Neoplasms/diagnosis
- Liver Neoplasms/drug therapy
- Liver Neoplasms/genetics
- Liver Neoplasms/mortality
- Molecular Targeted Therapy/methods
- Prognosis
- RNA, Long Noncoding/analysis
- RNA, Long Noncoding/antagonists & inhibitors
- RNA, Long Noncoding/genetics
- RNA, Long Noncoding/metabolism
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Affiliation(s)
- Zhao-Shan Niu
- Laboratory of Micromorphology, School of Basic Medicine, Medical Department of Qingdao University, Qingdao 266071, Shandong Province, China
| | - Xiao-Jun Niu
- Oncology Specialty, Medical Department of Qingdao University, Qingdao 266071, Shandong Province, China
| | - Wen-Hong Wang
- Department of Pathology, School of Basic Medicine, Medical Department of Qingdao University, Qingdao 266071, Shandong Province, China
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29
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Long Noncoding RNAs Act as Novel Biomarkers for Hepatocellular Carcinoma: Progress and Prospects. BIOMED RESEARCH INTERNATIONAL 2017; 2017:6049480. [PMID: 28835896 PMCID: PMC5557260 DOI: 10.1155/2017/6049480] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/04/2016] [Revised: 06/20/2017] [Accepted: 07/04/2017] [Indexed: 12/15/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and confers a poor prognosis. Novel diagnostic or prognostic biomarkers and effective therapeutic targets for HCCs are urgently needed. Currently, dozens of long noncoding RNAs (lncRNAs) have been identified as playing critical roles in cancer development and progression. Advanced studies have shown that several well-known lncRNAs are dysregulated in HCC tissue as compared to adjacent noncancerous tissue. Furthermore, highly stable cell-free circulating nucleic acids (cfCNAs), including lncRNAs, aberrantly expressed in the plasma of HCC patients, have been detected. In this review, we focus on the most extensively investigated lncRNAs in HCC and discuss the potential of HCC-related lncRNAs as novel biomarkers for early diagnosis and prognosis.
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30
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Abstract
Long noncoding RNAs (lncRNAs) are a relatively well-characterized class of noncoding RNA (ncRNA) molecules, involved in the regulation of various cell processes, including transcription, intracellular trafficking, and chromosome remodeling. Their deregulation has been associated with the development and progression of various cancer types, the fact which makes them suitable as biomarkers for cancer diagnosis and prognosis. In recent years, detection of cancer-associated lncRNAs in body fluids of cancer patients has proven itself as an especially valuable method to effectively diagnose cancer. Cancer diagnosis and prognosis employing circulating lncRNAs are preferential when compared to classical biopsies of tumor tissues, especially due to their noninvasiveness, and have great potential for routine usage in clinical practice. Thus, this review focuses on summarizing the perspectives of lncRNAs as biomarkers in cancer, based on evaluating their expression profiles determined in body fluids of cancer patients.
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31
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Hou Z, Xu X, Fu X, Tao S, Zhou J, Liu S, Tan D. HBx-related long non-coding RNA MALAT1 promotes cell metastasis via up-regulating LTBP3 in hepatocellular carcinoma. Am J Cancer Res 2017; 7:845-856. [PMID: 28469957 PMCID: PMC5411792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Accepted: 03/06/2017] [Indexed: 06/07/2023] Open
Abstract
Though it is widely known that hepatitis B virus X protein (HBx) is involved in the progression of hepatocellular carcinoma (HCC), the underlying mechanisms are not entirely clear. In recent years, metastasis associated with lung adenocarcinoma transcript 1 (MALAT1), which is an oncogenic long non-coding RNA (lncRNA), has been proved to be associated with many kinds of tumors, including liver cancer. In this study, we demonstrated that MALAT1 was involved in the HBx-mediated hepatocarcinogenesis. Firstly, we found that expression of MALAT1 was strongly up-regulated in HCC tissues and was directly proportional to the expression of HBx. Moreover, in HBx transfected LO2 and HepG2 cells, MALAT1 was also up-regulated compared with non-transfected cells. Then, we observed up-regulated MALAT1 in HepG2 cells could promote cell invasion and migration, whereas knockdown of MALAT1 in HBx-expressing hepatic cells (HepG2-HBx) resulted in a markedly inhibition of cell invasion and migration both in vitro and in vivo. To further obtain a deeper understanding of the effect of MALAT1, we took latent transforming growth factor β-binding protein 3 (LTBP3) into account by using several assays such as RNA interference, luciferase, transwell and wound healing. Results showed that MALAT1 could promote tumor growth and metastasis by activating LTBP3, which could also be up-regulated by HBx. Meanwhile, the similar results were detected in nude mice. These findings could demonstrate an important mechanism of hepatocarcinogenesis through the signaling of HBx-MALAT1/LTBP3 axis, and may give a potential target for treatment of HCC.
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Affiliation(s)
- Zhouhua Hou
- Department of Infectious Disease, Xiangya Hospital, Central South UniversityChangsha 410008, P. R. China
| | - Xuwen Xu
- Department of Infectious Disease, Xiangya Hospital, Central South UniversityChangsha 410008, P. R. China
| | - Xiaoyu Fu
- Department of Infectious Disease, Xiangya Hospital, Central South UniversityChangsha 410008, P. R. China
| | - Shuhui Tao
- Department of Infectious Disease, Xiangya Hospital, Central South UniversityChangsha 410008, P. R. China
| | - Jiebin Zhou
- Department of Infectious Disease, Xiangya Hospital, Central South UniversityChangsha 410008, P. R. China
| | - Shuiping Liu
- Department of Infectious Disease, Xiangya Hospital, Central South UniversityChangsha 410008, P. R. China
- Department of Microbiology, Xiangya Medical College, Central South UniversityChangsha 410008, P. R. China
| | - Deming Tan
- Department of Infectious Disease, Xiangya Hospital, Central South UniversityChangsha 410008, P. R. China
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32
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Smekalova EM, Kotelevtsev YV, Leboeuf D, Shcherbinina EY, Fefilova AS, Zatsepin TS, Koteliansky V. lncRNA in the liver: Prospects for fundamental research and therapy by RNA interference. Biochimie 2016; 131:159-172. [DOI: 10.1016/j.biochi.2016.06.007] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2016] [Accepted: 06/14/2016] [Indexed: 12/19/2022]
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33
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Identification of long noncoding RNA expression profile in oxaliplatin-resistant hepatocellular carcinoma cells. Gene 2016; 596:53-88. [PMID: 27729273 DOI: 10.1016/j.gene.2016.10.008] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2016] [Revised: 09/23/2016] [Accepted: 10/05/2016] [Indexed: 12/18/2022]
Abstract
Hepatocellular carcinoma (HCC) is the most prevalent and malignant type of liver cancer. Besides the high incidence, the resistance to chemotherapy is a major problem that leads to the high mortality of HCC. Recently, aberrant expression of long noncoding RNAs (lncRNAs) has been considered as a primary feature of many types of cancer. However, the genome-wide expression pattern and associated functional implications of lncRNAs in chemo-resistant HCC cells remain unknown. In this study, we identified 120 differentially expressed lncRNAs with 61 up-regulated and 59 down-regulated (fold change>2, p<0.05) along with 421 differentially expressed mRNAs with 228 up-regulated and 193 down-regulated (fold change>2, p<0.05) in oxaliplatin-resistant (MHCC97H-OXA) HCC cells, compared to parental oxaliplatin-sensitive (MHCC97H) by microarray. The underlying pathways were related to cell death, proliferation, cellular response to stimulus, including p53 pathway, ErbB pathway and MAPK pathway. Further, 16 lncRNAs were selected for validation of microarray results with quantitative PCR, and a strong correlation was identified between the qPCR results and microarray data. We demonstrated for the first time that ENST00000438347, NR_073453 and ENST00000502804 were up-regulated in MHCC97H-OXA cells as well as chemo-resistant HCC cancerous tissues. Moreover, the expression of ENST00000518376 was significantly associated with the tumor size and differentiation. Overall survival analysis showed that high expression of ENST00000438347 and ENST00000518376 was associated with poor prognosis in HCC patients. Taken together, our results reveal that the expression profile in oxaliplatin-resistant HCC is significantly altered including lncRNAs. And a series of de novo lncRNAs play important functions in HCC oxaliplatin resistance and HCC progression.
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34
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Long non-coding RNA Unigene56159 promotes epithelial-mesenchymal transition by acting as a ceRNA of miR-140-5p in hepatocellular carcinoma cells. Cancer Lett 2016; 382:166-175. [PMID: 27597739 DOI: 10.1016/j.canlet.2016.08.029] [Citation(s) in RCA: 111] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2016] [Revised: 08/30/2016] [Accepted: 08/31/2016] [Indexed: 12/19/2022]
Abstract
HBV infection has been reported to be closely associated with HCC development; however, the underlying mechanisms are unclear. Emerging evidence has indicated that long non-coding RNAs (lncRNAs) play important regulatory roles in the pathogenesis and progression of cancers. To investigate the important role and mechanism of lncRNAs in the progression of HBV-related HCC, we screened lncRNAs in HBV-positive and HBV-negative HCC tissues. We identified a novel lncRNA, lncRNA-Unigene56159, which is highly expressed in HBV-related HCC tissues, and further analysis showed that this lncRNA was induced by HBV in vitro. Functionally, Unigene56159 significantly promoted cell migration/invasion and epithelial-mesenchymal transition (EMT) in HCC. Mechanistically, Unigene56159 could directly bind to miR-140-5p and effectively act as a competing endogenous RNA (ceRNA) for miR-140-5p to de-repress the expression of the target gene Slug. Collectively, our findings indicate that the Unigene56159/miR-140-5p/Slug axis contributes to HCC cell migration and invasion, which may provide novel insights into the function of lncRNA-driven hepatocarcinogenesis.
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35
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Shi L, Peng F, Tao Y, Fan X, Li N. Roles of long noncoding RNAs in hepatocellular carcinoma. Virus Res 2016; 223:131-9. [PMID: 27374059 DOI: 10.1016/j.virusres.2016.06.008] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Revised: 05/19/2016] [Accepted: 06/15/2016] [Indexed: 12/11/2022]
Abstract
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with high prevalence and lethality. Hepatitis B virus (HBV) and Hepatitis C virus (HCV) infection are the major risk factors for HCC. Long noncoding RNAs (lncRNAs) are involved in diverse biological processes, and aberrant lncRNA expression is relevant to many human diseases including HCC. Although many researches on HCC have been reported and lncRNAs roles in carcinogenesis have been highlighted recently, reports on roles of lncRNAs in HBV/HCV-induced HCC are limited. In this review, we concentrate on recent progress regarding the functional roles of lncRNAs in HCC and HBV/HCV-related HCC.
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Affiliation(s)
- Linxi Shi
- Department of Blood Transfusion, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan Province 410008, China
| | - Fang Peng
- Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, China
| | - Yongguang Tao
- Cancer Research Institute, Central South University, 87 Xiangya Road, Changsha, Hunan 410078, China
| | - Xuegong Fan
- Hunan Key Laboratory of Viral Hepatitis,Xiangya Hospital, Central South University, Hunan Province, 87 Xiangya Road, Changsha 410008, China.
| | - Ning Li
- Department of Blood Transfusion, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, Hunan Province 410008, China.
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36
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Li S, Zheng L. Effect of Combined Treatment Using Wilfortrine and Paclitaxel in Liver Cancer and Related Mechanism. Med Sci Monit 2016; 22:1109-14. [PMID: 27043783 PMCID: PMC4822940 DOI: 10.12659/msm.896197] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022] Open
Abstract
Background Liver cancer is a common malignant tumor with high mortality. Currently, effective medicines against liver cancer are still lacking. Paclitaxel is a wide-spectrum anti-tumor agent, while wilfortrine has been shown to have an inhibitory effect on the proliferation of liver cancer cells. This study thus investigated the potential effect of paclitaxel combined with wilfortrine on cultured liver cancer cells and related mechanisms, in order to provide evidence for pathogenesis and treatment of liver cancer. Material/Methods Liver cancer cell line HpeG2 was divided into control, paclitaxel, wilfortrine, and combined treatment groups. Cell proliferation was tested by MTT, while invasion was detected in Transwell chamber assay. Apoptotic protein Bcl-2 and Bax expression levels were further quantified using real-time PCR and Western blotting. Results Both of those 2 drugs can effectively inhibit cancer cell proliferation, depress invasion ability, increase Bcl-2 expression, and elevate Bax expression levels (p<0.05 in all cases). The combined therapy had better treatment efficacy compared to either of those drugs alone (p<0.05). Conclusions The combined treatment using wilfortrine and paclitaxel can inhibit proliferation and invasion of liver cancer cells via down-regulating Bcl-2 and up-regulating Bax, with better efficacy than single use of either drug.
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Affiliation(s)
- Shuzhen Li
- Department of Pharmacy, Shandong Traffic Hospital, Jinan, Shandong, China (mainland)
| | - Lei Zheng
- Department of Pharmacy, Shandong Traffic Hospital, Jinan, Shandong, China (mainland)
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37
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Bayoumi AS, Sayed A, Broskova Z, Teoh JP, Wilson J, Su H, Tang YL, Kim IM. Crosstalk between Long Noncoding RNAs and MicroRNAs in Health and Disease. Int J Mol Sci 2016; 17:356. [PMID: 26978351 PMCID: PMC4813217 DOI: 10.3390/ijms17030356] [Citation(s) in RCA: 188] [Impact Index Per Article: 20.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2016] [Revised: 02/29/2016] [Accepted: 03/02/2016] [Indexed: 02/06/2023] Open
Abstract
Protein-coding genes account for only a small part of the human genome; in fact, the vast majority of transcripts are comprised of non-coding RNAs (ncRNAs) including long ncRNAs (lncRNAs) and small ncRNAs, microRNAs (miRs). Accumulating evidence indicates that ncRNAs could play critical roles in regulating many cellular processes which are often implicated in health and disease. For example, ncRNAs are aberrantly expressed in cancers, heart diseases, and many other diseases. LncRNAs and miRs are therefore novel and promising targets to be developed into biomarkers for diagnosis and prognosis as well as treatment options. The interaction between lncRNAs and miRs as well as its pathophysiological significance have recently been reported. Mechanistically, it is believed that lncRNAs exert “sponge-like” effects on various miRs, which subsequently inhibits miR-mediated functions. This crosstalk between two types of ncRNAs frequently contributes to the pathogenesis of the disease. In this review, we provide a summary of the recent studies highlighting the interaction between these ncRNAs and the effects of this interaction on disease pathogenesis and regulation.
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Affiliation(s)
- Ahmed S Bayoumi
- Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
| | - Amer Sayed
- Department of Internal Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
| | - Zuzana Broskova
- Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
| | - Jian-Peng Teoh
- Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
| | - James Wilson
- Department of Internal Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
| | - Huabo Su
- Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
| | - Yao-Liang Tang
- Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
| | - Il-Man Kim
- Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
- Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
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