|
1
|
Luo Y, Zhang Q, Shao C, Li J, Chen J, Han L, Jiang X, Hong L. Diagnostic value of LncRNA SNHG16 for osteoporotic fractures and its potential regulation of fracture healing. Hereditas 2025; 162:54. [PMID: 40197315 PMCID: PMC11974092 DOI: 10.1186/s41065-025-00423-6] [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: 02/17/2025] [Accepted: 03/25/2025] [Indexed: 04/10/2025] Open
Abstract
BACKGROUND Osteoporotic fractures (OPF) have a serious impact on the health of patients. It is of great importance to investigate the diagnostic effect of SNH16 on OPF and the mechanism of action to promote fracture healing. METHODS 132 OPF patients and 128 OP patients were included. The levels of SNHG16, Col I, RUNX2 and OCN were evaluated by RT-qPCR. The diagnostic value of SNHG16 was evaluated by ROC curve. Cell proliferation ability was assessed by CCK-8, and apoptosis rate was detected by flow cytometry. ENCORI was used to predict the binding sites of SNHG16 with downstream target genes. DLR assay demonstrated the targeting relationship between SNHG16 and miR-432-5p. RESULTS SNHG16 was poorly expressed in OPF patients compared with OP patients, and its expression was lower in patients with delayed healing. In addition, in the OPF, OPG level was decreased, the level of RANKL was increased, and the balance of bone resorption formation is disrupted leading to fractures. Knockdown of SNHG16 results in decreased cell proliferation and increased apoptosis, and high SNHG16 expression decreases miR-432-5p expression, thereby increasing the levels of Col I, RUNX2 and OCN. CONCLUSION Increasing SNHG16 can reduce the level of miR-432-5p thereby increasing the level of osteosynthesis proteins and restoring cellular activity, thereby promoting fracture healing.
Collapse
Affiliation(s)
- Yuanming Luo
- Department of Orthopedics, The Affiliated Hospital of Jiaxing University, Jiaxing, 314001, China
| | - Qingfeng Zhang
- Department of Spine, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, 100029, China
| | - Changqing Shao
- Department of Orthopedics, Xuzhou Central Hospital, Xuzhou, 221009, China
| | - Jin Li
- Department of Rehabilitation, Xuzhou Central Hospital, Xuzhou, 221009, China
- Department of Rehabilitation, Xuzhou Rehabilitation Hospital, Xuzhou, 220005, China
| | - Jiaojiao Chen
- Department of Rehabilitation, Xuzhou Central Hospital, Xuzhou, 221009, China
- Department of Rehabilitation, Xuzhou Rehabilitation Hospital, Xuzhou, 220005, China
| | - Liang Han
- Department of Rehabilitation, Xuzhou Central Hospital, Xuzhou, 221009, China
- Department of Rehabilitation, Xuzhou Rehabilitation Hospital, Xuzhou, 220005, China
| | - Xiaowei Jiang
- Department of Rehabilitation, Xuzhou Central Hospital, Xuzhou, 221009, China
- Department of Rehabilitation, Xuzhou Rehabilitation Hospital, Xuzhou, 220005, China
| | - Li Hong
- Department of Laboratory, Haikou Hospital of the Maternal and Child Health, No. 6, Wentan Road, Guoxing Avenue, Qiongshan District, Haikou, 570102, China.
| |
Collapse
|
|
2
|
Zhou M, Tian M, Li Z, Wang C, Guo Z. Overview of splicing variation in ovarian cancer. Biochim Biophys Acta Rev Cancer 2025; 1880:189288. [PMID: 39993511 DOI: 10.1016/j.bbcan.2025.189288] [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: 10/14/2024] [Revised: 02/14/2025] [Accepted: 02/14/2025] [Indexed: 02/26/2025]
Abstract
Ovarian cancer remains one of the deadliest gynecological malignancies, with a persistently high mortality rate despite promising advancements in immunotherapy. Aberrant splicing events play a crucial role in cancer heterogeneity and treatment resistance. Many splicing variants, especially those involving key molecular markers such as BRCA1/2, are closely linked to disease progression and treatment outcomes. These variants and related splicing factors hold significant clinical value as diagnostic and prognostic biomarkers and therapeutic targets. This review provides a comprehensive overview of splicing variants in ovarian cancer, emphasizing their role in metastasis and resistance, and offers insights to advance biomarker development and treatment strategies.
Collapse
Affiliation(s)
- Min Zhou
- From the Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Mengdie Tian
- From the Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Zhuoer Li
- From the Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Chunli Wang
- From the Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University, Shenyang, China
| | - Zhiqiang Guo
- From the Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University, Shenyang, China.
| |
Collapse
|
|
3
|
Yang TF, Li XR, Kong MW. Molecular mechanisms underlying roles of long non-coding RNA small nucleolar RNA host gene 16 in digestive system cancers. World J Gastrointest Oncol 2024; 16:4300-4308. [PMID: 39554746 PMCID: PMC11551640 DOI: 10.4251/wjgo.v16.i11.4300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2024] [Revised: 06/13/2024] [Accepted: 07/02/2024] [Indexed: 10/25/2024] Open
Abstract
This editorial reviews the molecular mechanisms underlying the roles of the long non-coding RNA (lncRNA) small nucleolar RNA host gene 16 (SNHG16) in digestive system cancers based on two recent studies on lncRNAs in digestive system tumors. The first study, by Zhao et al, explored how hBD-1 affects colon cancer, via the lncRNA TCONS_00014506, by inhibiting mTOR and promoting autophagy. The second one, by Li et al, identified the lncRNA prion protein testis specific (PRNT) as a factor in oxaliplatin resistance by sponging ZNF184 to regulate HIPK2 and influence colorectal cancer progression and chemoresistance, suggesting PRNT as a potential therapeutic target for colorectal cancer. Both of these two articles discuss the mechanisms by which lncRNAs contribute to the development and progression of digestive system cancers. As a recent research hotspot, SNHG16 is a typical lncRNA that has been extensively studied for its association with digestive system cancers. The prevailing hypothesis is that SNHG16 participates in the development and progression of digestive system tumors by acting as a competing endogenous RNA, interacting with other proteins, regulating various genes, and affecting downstream target molecules. This review systematically examines the recently reported biological functions, related molecular mechanisms, and potential clinical significance of SNHG16 in various digestive system cancers, and explores the relationship between SNHG16 and digestive system cancers. The findings suggest that SNHG16 may serve as a potential biomarker and therapeutic target for human digestive system cancers.
Collapse
Affiliation(s)
- Ting-Fang Yang
- Department of Oncology, Guiqian International General Hospital, Guiyang 550018, Guizhou Province, China
| | - Xin-Rui Li
- Department of Cardiology, Guiqian International General Hospital, Guiyang 550018, Guizhou Province, China
| | - Mo-Wei Kong
- Department of Cardiology, Guiqian International General Hospital, Guiyang 550018, Guizhou Province, China
| |
Collapse
|
|
4
|
Zhao L, Kan Y, Wang L, Pan J, Li Y, Zhu H, Yang Z, Xiao L, Fu X, Peng F, Ren H. Roles of long non‑coding RNA SNHG16 in human digestive system cancer (Review). Oncol Rep 2024; 52:106. [PMID: 38940337 PMCID: PMC11234248 DOI: 10.3892/or.2024.8765] [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: 05/23/2023] [Accepted: 04/26/2024] [Indexed: 06/29/2024] Open
Abstract
The incidence of tumors in the human digestive system is relatively high, including esophageal cancer, liver cancer, pancreatic cancer, gastric cancer and colorectal cancer. These malignancies arise from a complex interplay of environmental and genetic factors. Among them, long non‑coding RNAs (lncRNAs), which cannot be translated into proteins, serve an important role in the development, progression, migration and prognosis of tumors. Small nucleolar RNA host gene 16 (SNHG16) is a typical lncRNA, and its relationship with digestive system tumors has been widely explored. The prevailing hypothesis suggests that the principal molecular mechanism of SNHG16 in digestive system tumors involves it functioning as a competitive endogenous RNA that interacts with other proteins, regulates various genes and influences a downstream target molecule. The present review summarizes recent research on the relationship between SNHG16 and numerous types of digestive system cancer, encompassing its biological functions, underlying mechanisms and potential clinical implications. Furthermore, it outlines the association between SNHG16 expression and pertinent risk factors, such as smoking, infection and diet. The present review indicated the promise of SNHG16 as a potential biomarker and therapeutic target in human digestive system cancer.
Collapse
Affiliation(s)
- Lujie Zhao
- School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Yuling Kan
- Central Laboratory of Binzhou People's Hospital, Binzhou, Shandong 256600, P.R. China
| | - Lu Wang
- School of Clinical Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Jiquan Pan
- School of Clinical Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Yun Li
- School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Haiyan Zhu
- Department of Medical Oncology, Weifang People's Hospital, Weifang, Shandong 261000, P.R. China
- Department of Medical Oncology, The First Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Zhongfa Yang
- School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Lin Xiao
- School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Xinhua Fu
- School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Fujun Peng
- School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
- Weifang Key Laboratory of Collaborative Innovation of Intelligent Diagnosis and Treatment and Molecular Diseases, School of Basic Medical Sciences, Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| | - Haipeng Ren
- Department of Medical Oncology, Weifang People's Hospital, Weifang, Shandong 261000, P.R. China
- Department of Medical Oncology, The First Affiliated Hospital of Shandong Second Medical University, Weifang, Shandong 261053, P.R. China
| |
Collapse
|
|
5
|
Ye H, Li MY, Shi RH. Advances in understanding of mechanism of long non-coding RNA SNHG16 in digestive system tumors. WORLD CHINESE JOURNAL OF DIGESTOLOGY 2024; 32:405-411. [DOI: 10.11569/wcjd.v32.i6.405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/29/2024]
|
|
6
|
Jalali P, Yaghoobi A, Rezaee M, Zabihi MR, Piroozkhah M, Aliyari S, Salehi Z. Decoding common genetic alterations between Barrett's esophagus and esophageal adenocarcinoma: A bioinformatics analysis. Heliyon 2024; 10:e31194. [PMID: 38803922 PMCID: PMC11128929 DOI: 10.1016/j.heliyon.2024.e31194] [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: 11/08/2023] [Revised: 05/12/2024] [Accepted: 05/13/2024] [Indexed: 05/29/2024] Open
Abstract
Background Esophageal adenocarcinoma (EAC) is a common cancer with a poor prognosis in advanced stages. Therefore, early EAC diagnosis and treatment have gained attention in recent decades. It has been found that various pathological changes, particularly Barrett's Esophagus (BE), can occur in the esophageal tissue before the development of EAC. In this study, we aimed to identify the molecular contributor in BE to EAC progression by detecting the essential regulatory genes that are differentially expressed in both BE and EAC. Materials and methods We conducted a comprehensive bioinformatics analysis to detect BE and EAC-associated genes. The common differentially expressed genes (DEGs) and common single nucleotide polymorphisms (SNPs) were detected using the GEO and DisGeNET databases, respectively. Then, hub genes and the top modules within the protein-protein interaction network were identified. Moreover, the co-expression network of the top module by the HIPPIE database was constructed. Additionally, the gene regulatory network was constructed based on miRNAs and circRNAs. Lastly, we inspected the DGIdb database for possible interacted drugs. Results Our microarray dataset analysis identified 92 common DEGs between BE and EAC with significant enrichment in skin and epidermis development genes. The study also identified 22 common SNPs between BE and EAC. The top module of PPI network analysis included SCEL, KRT6A, SPRR1A, SPRR1B, SPRR3, PPL, SPRR2B, EVPL, and CSTA. We constructed a ceRNA network involving three specific mRNAs, 23 miRNAs, and 101 selected circRNAs. According to the results from the DGIdb database, TD101 was found to interact with the KRT6A gene. Conclusion The present study provides novel potential candidate genes that may be involved in the molecular association between Esophageal adenocarcinoma and Barrett's Esophagus, resulting in developing the diagnostic tools and therapeutic targets to prevent progression of BE to EAC.
Collapse
Affiliation(s)
- Pooya Jalali
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Alireza Yaghoobi
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Malihe Rezaee
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zabihi
- Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Moein Piroozkhah
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shahram Aliyari
- Division of Applied Bioinformatics, German Cancer Research Center DKFZ Heidelberg, Iran
| | - Zahra Salehi
- Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
- Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
7
|
Saeinasab M, Atlasi Y, M Matin M. Functional role of lncRNAs in gastrointestinal malignancies: the peculiar case of small nucleolar RNA host gene family. FEBS J 2024; 291:1353-1385. [PMID: 36282516 DOI: 10.1111/febs.16668] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Revised: 09/18/2022] [Accepted: 10/24/2022] [Indexed: 11/06/2022]
Abstract
Long noncoding RNAs (lncRNAs) play crucial roles in normal physiology and are often de-regulated in disease states such as cancer. Recently, a class of lncRNAs referred to as the small nucleolar RNA host gene (SNHG) family have emerged as important players in tumourigenesis. Here, we discuss new findings describing the role of SNHGs in gastrointestinal tumours and summarize the three main functions by which these lncRNAs promote carcinogenesis, namely: competing with endogenous RNAs, modulating protein function, and regulating epigenetic marking. Furthermore, we discuss how SNHGs participate in different hallmarks of cancer, and how this class of lncRNAs may serve as potential biomarkers in cancer diagnosis and therapy.
Collapse
Affiliation(s)
- Morvarid Saeinasab
- Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Iran
| | - Yaser Atlasi
- Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, UK
| | - Maryam M Matin
- Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Iran
- Novel Diagnostics and Therapeutics Research Group, Institute of Biotechnology, Ferdowsi University of Mashhad, Iran
| |
Collapse
|
|
8
|
Wei QY, Jin F, Wang ZY, Li BJ, Cao WB, Sun ZY, Mo SJ. MicroRNAs: A novel signature in the metastasis of esophageal squamous cell carcinoma. World J Gastroenterol 2024; 30:1497-1523. [PMID: 38617454 PMCID: PMC11008420 DOI: 10.3748/wjg.v30.i11.1497] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 01/12/2024] [Accepted: 03/01/2024] [Indexed: 03/21/2024] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is a malignant epithelial tumor, characterized by squamous cell differentiation, it is the sixth leading cause of cancer-related deaths globally. The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered, coupled with higher risk of metastasis, which is an exceedingly malignant characteristic of cancer, frequently leading to a high mortality rate. Unfortunately, there is currently no specific and effective marker to predict and treat metastasis in ESCC. MicroRNAs (miRNAs) are a class of small non-coding RNA molecules, approximately 22 nucleotides in length. miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence, progression, and prognosis of cancer. Here, we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis, and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors. This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis, with the ultimate aim of reducing the mortality rate among patients with ESCC.
Collapse
Affiliation(s)
- Qi-Ying Wei
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Feng Jin
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Zhong-Yu Wang
- Department of Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Bing-Jie Li
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Wen-Bo Cao
- Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Zhi-Yan Sun
- Division of Special Service, Department of Basic Oncology, School of Basic Medicine, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| | - Sai-Jun Mo
- Department of Basic Science of Oncology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan Province, China
| |
Collapse
|
|
9
|
Ghahramani Almanghadim H, Karimi B, Poursalehi N, Sanavandi M, Atefi Pourfardin S, Ghaedi K. The biological role of lncRNAs in the acute lymphocytic leukemia: An updated review. Gene 2024; 898:148074. [PMID: 38104953 DOI: 10.1016/j.gene.2023.148074] [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: 10/10/2023] [Revised: 11/29/2023] [Accepted: 12/08/2023] [Indexed: 12/19/2023]
Abstract
The cause of leukemia, a common malignancy of the hematological system, is unknown. The structure of long non-coding RNAs (lncRNAs) is similar to mRNA but no ability to encode proteins. Numerous malignancies, including different forms of leukemia, are linked to Lnc-RNAs. It is verified that the carcinogenesis and growth of a variety of human malignancies are significantly influenced by aberrant lncRNA expression. The body of evidence linking various types of lncRNAs to the etiology of leukemia has dramatically increased during the past ten years. Some lncRNAs are therefore anticipated to function as novel therapeutic targets, diagnostic biomarkers, and clinical outcome predictions. Additionally, these lncRNAs may provide new therapeutic options and insight into the pathophysiology of diseases, particularly leukemia. Thus, this review outlines the present comprehension of leukemia-associated lncRNAs.
Collapse
Affiliation(s)
| | - Bahareh Karimi
- Department of Cellular and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
| | - Negareh Poursalehi
- Department of Medical Biotechnology, School of Medicine Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | | | | | - Kamran Ghaedi
- Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Hezar Jerib Ave., Azadi Sq., 81746-73441 Isfahan, Iran.
| |
Collapse
|
|
10
|
Hou W, Xu L, Su T, Wu Y, Liu Y, Wei Y. Hypoxia Induces Tumor-Derived Exosome SNHG16 to Mediate Nasopharyngeal Carcinoma Progression through the miR-23b-5p/MCM6 Pathway. Appl Biochem Biotechnol 2024; 196:275-295. [PMID: 37119503 DOI: 10.1007/s12010-023-04558-y] [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] [Accepted: 04/18/2023] [Indexed: 05/01/2023]
Abstract
This study aims to investigate the mechanism of tumor-derived exosomal (EVs) SNHG16 in promoting the progression of nasopharyngeal carcinoma (NPC). QRT-PCR was used to detect the expression of SNHG16, miR-23b-5p and MCM6 in NPC. MTT, flow cytometry and transwell were used to detect the effects of them on the proliferation, cycle, apoptosis and invasion ability of NPC. Transmission electron microscopy, Western blotting and BCA were used to verify the regulation of exosome secretion under different oxygen environments. Our results showed that hypoxia induces tumor-derived exosome SNHG16 to mediate NPC progression through the miR-23b-5p/MCM6 pathway.
Collapse
Affiliation(s)
- Wei Hou
- Department of Otolaryngology, The Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, 712000, Shaanxi, China
| | - Lu Xu
- Department of Otolaryngology, The Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, 712000, Shaanxi, China
| | - Tao Su
- Department of Otolaryngology, The Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, 712000, Shaanxi, China
| | - Yunxiao Wu
- Department of Neurology, Yang Ling Demonstration Zone Hospital, Yangling, 712100, Shaanxi, China
| | - Yujuan Liu
- Department of Otolaryngology, Yang Ling Demonstration Zone Hospital, Yangling, 712100, Shaanxi, China
| | - Yangao Wei
- Department of Otolaryngology, Yang Ling Demonstration Zone Hospital, Yangling, 712100, Shaanxi, China.
| |
Collapse
|
|
11
|
Pang L, Wang Q, Wang L, Hu Z, Yang C, Li Y, Wang Z, Li Y. Development and validation of cuproptosis-related lncRNA signatures for prognosis prediction in colorectal cancer. BMC Med Genomics 2023; 16:58. [PMID: 36949429 PMCID: PMC10031908 DOI: 10.1186/s12920-023-01487-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Accepted: 03/11/2023] [Indexed: 03/24/2023] Open
Abstract
BACKGROUND Cuproptosis, a novel form of programmed cell death, plays an essential role in various cancers. However, studies of the function of cuproptosis lncRNAs (CRLs) in colorectal cancer (CRC) remain limited. Thus, this study aims to identify the cuprotosis-related lncRNAs (CRLs) in CRC and to construct the potential prognostic CRLs signature model in CRC. METHODS First, we downloaded RNA-Seq data and clinical information of CRC patients from TCGA database and obtained the prognostic CRLs based on typical expression analysis of cuproptosis-related genes (CRGs) and univariate Cox regression. Then, we constructed a prognostic model using the Least Absolute Shrinkage and Selection Operator algorithm combined with multiple Cox regression methods (Lasso-Cox). Next, we generated Kaplan-Meier survival and receiver operating characteristic curves to estimate the performance of the prognostic model. In addition, we also analysed the relationships between risk signatures and immune infiltration, mutation, and drug sensitivity. Finally, we performed quantitative reverse transcription polymerase chain reaction (qRT -PCR) to verify the prognostic model. RESULT Lasso-Cox analysis revealed that four CRLs, SNHG16, LENG8-AS1, LINC0225, and RPARP-AS1, were related to CRC prognosis. Receiver operating characteristic (ROC) and Kaplan-Meier analysis curves indicated that this model performs well in prognostic predictions of CRC patients. The DCA results also showed that the model included four gene signatures was better than the traditional model. In addition, GO and KEGG analyses revealed that DE-CRLs are enriched in critical signalling pathway, such as chemical carcinogenesis-DNA adducts and basal cell carcinoma. Immune infiltration analysis revealed significant differences in immune infiltration cells between the high-risk and low-risk groups. Furthermore, significant differences in somatic mutations were noted between the high-risk and low-risk groups. Finally, we also validated the expression of four CRLs in FHCs cell lines and CRC cell lines using qRT-PCR. CONCLUSION The signature composed of SNHG16, LENG8-AS1, LINC0225, and RPARP-AS1, which has better performance in predicting colorectal cancer prognosis and are promising biomarkers for prognosis prediction of CRC.
Collapse
Affiliation(s)
- Lin Pang
- Department of Colorectal and Anal Surgery, The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan, 030012, China
- Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, 030001, China
| | - Qingqing Wang
- Department of Health Statistics, School of Public Health, Shanxi Medical University, Taiyuan, 030001, China
| | - Lingxiao Wang
- Department of Colorectal and Anal Surgery, The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan, 030012, China
| | - Zhen Hu
- Department of Colorectal and Anal Surgery, The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan, 030012, China
| | - Chong Yang
- Department of Colorectal and Anal Surgery, The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan, 030012, China
| | - Yiqun Li
- Department of Colorectal and Anal Surgery, The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan, 030012, China
| | - Zhenqi Wang
- Department of Colorectal and Anal Surgery, The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan, 030012, China
| | - Yaoping Li
- Department of Colorectal and Anal Surgery, The Fifth Clinical Medical College of Shanxi Medical University, Taiyuan, 030012, China.
| |
Collapse
|
|
12
|
Zhu Y, Zhang F, Zhang S, Yi M. Predicting latent lncRNA and cancer metastatic event associations via variational graph auto-encoder. Methods 2023; 211:1-9. [PMID: 36709790 DOI: 10.1016/j.ymeth.2023.01.006] [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: 10/20/2022] [Revised: 12/05/2022] [Accepted: 01/20/2023] [Indexed: 01/27/2023] Open
Abstract
Long non-coding RNA (lncRNA) are shown to be closely associated with cancer metastatic events (CME, e.g., cancer cell invasion, intravasation, extravasation, proliferation) that collaboratively accelerate malignant cancer spread and cause high mortality rate in patients. Clinical trials may accurately uncover the relationships between lncRNAs and CMEs; however, it is time-consuming and expensive. With the accumulation of data, there is an urgent need to find efficient ways to identify these relationships. Herein, a graph embedding representation-based predictor (VGEA-LCME) for exploring latent lncRNA-CME associations is introduced. In VGEA-LCME, a heterogeneous combined network is constructed by integrating similarity and linkage matrix that can maintain internal and external characteristics of networks, and a variational graph auto-encoder serves as a feature generator to represent arbitrary lncRNA and CME pair. The final robustness predicted result is obtained by ensemble classifier strategy via cross-validation. Experimental comparisons and literature verification show better remarkable performance of VGEA-LCME, although the similarities between CMEs are challenging to calculate. In addition, VGEA-LCME can further identify organ-specific CMEs. To the best of our knowledge, this is the first computational attempt to discover the potential relationships between lncRNAs and CMEs. It may provide support and new insight for guiding experimental research of metastatic cancers. The source code and data are available at https://github.com/zhuyuan-cug/VGAE-LCME.
Collapse
Affiliation(s)
- Yuan Zhu
- School of Automation, China University of Geosciences, 388 Lumo Road, Hongshan District, 430074, Wuhan, Hubei, China; Hubei Key Laboratory of Advanced Control and Intelligent Automation for Complex Systems, 388 Lumo Road, Hongshan District, 430074, Wuhan, Hubei, China; Engineering Research Center of Intelligent Technology for Geo-Exploration, 388 Lumo Road, Hongshan District, 430074, Wuhan, Hubei, China
| | - Feng Zhang
- School of Mathematics and Physics, China University of Geosciences, 388 Lumo Road, Hongshan District, 430074, Wuhan, Hubei, China
| | - Shihua Zhang
- College of Life Science and Health, Wuhan University of Science and Technology, 974 Heping Avenue, Qingshan District, 430081, Wuhan, Hubei, China.
| | - Ming Yi
- School of Mathematics and Physics, China University of Geosciences, 388 Lumo Road, Hongshan District, 430074, Wuhan, Hubei, China.
| |
Collapse
|
|
13
|
Ren L, Fang X, Shrestha SM, Ji Q, Ye H, Liang Y, Liu Y, Feng Y, Dong J, Shi R. LncRNA SNHG16 promotes development of oesophageal squamous cell carcinoma by interacting with EIF4A3 and modulating RhoU mRNA stability. Cell Mol Biol Lett 2022; 27:89. [PMID: 36221055 PMCID: PMC9552503 DOI: 10.1186/s11658-022-00386-w] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 09/09/2022] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND Numerous studies have revealed that long noncoding RNAs (lncRNAs) are closely related to the development of many diseases and carcinogenesis. However, their specific biological function and molecular mechanism in oesophageal squamous cell carcinoma (ESCC) remains unclear. METHODS RNA-Seq was performed to determine the differential expressions of lncRNAs in ESCC, and the level of SNHG16 expression was detected in ESCC and intraepithelial neoplasia (IEN) samples. In vitro and in vivo experiments were performed to explore the role of SNHG16 and the interaction of EIF4A3 and Ras homologue family member U (RhoU) signalling. RESULTS One hundred and seventy-five upregulated and 134 downregulated lncRNAs were identified by RNA-Seq. SNHG16 was highly expressed in ESCC and intraepithelial neoplasia (IEN) samples, and its expression level was correlated with tumour differentiation and T stage. Overexpression of SNHG16 can facilitate ESCC cell proliferation and metastasis. Mechanistically, we noticed that SNHG16 could bind RNA binding protein (RBP)-eukaryotic translation initiation factor (EIF4A3) and interact with it to form a complex. Importantly, the coalition of SNHG16 and EIF4A3 ultimately regulated Ras homologue family member U (RhoU). SNHG16 modulated RhoU expression by recruiting EIF4A3 to regulate the stability of RhoU mRNA. Knockdown of RhoU further alleviated the effect of the SNHG16 oncogene in ESCC cells. CONCLUSIONS The newly identified SNHG16-EIF4A3-RhoU signalling pathway directly coordinates the response in ESCC pathogenesis and suggests that SNHG16 is a promising target for potential ESCC treatment.
Collapse
Affiliation(s)
- Lihua Ren
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, Jiangsu Province, People's Republic of China
| | - Xin Fang
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, Jiangsu Province, People's Republic of China
| | - Sachin Mulmi Shrestha
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, Jiangsu Province, People's Republic of China
| | - Qinghua Ji
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, Jiangsu Province, People's Republic of China
| | - Hui Ye
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, Jiangsu Province, People's Republic of China
| | - Yan Liang
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, Jiangsu Province, People's Republic of China
| | - Yang Liu
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, Jiangsu Province, People's Republic of China
| | - Yadong Feng
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, Jiangsu Province, People's Republic of China
| | - Jingwu Dong
- Department of Gastroenterology, Xuyi County People's Hospital, Huaian, 211700, People's Republic of China
| | - Ruihua Shi
- Department of Gastroenterology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, Jiangsu Province, People's Republic of China.
| |
Collapse
|
|
14
|
Sun W, Zhang X, He X, Zhang J, Wang X, Lin W, Wang X, Wu X. Long non-coding RNA SNHG16 silencing inhibits proliferation and inflammation in Mycobacterium tuberculosis-infected macrophages by targeting miR-140-5p expression. INFECTION, GENETICS AND EVOLUTION : JOURNAL OF MOLECULAR EPIDEMIOLOGY AND EVOLUTIONARY GENETICS IN INFECTIOUS DISEASES 2022; 103:105325. [PMID: 35779785 DOI: 10.1016/j.meegid.2022.105325] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 06/23/2022] [Accepted: 06/26/2022] [Indexed: 06/15/2023]
Abstract
OBJECTIVE The study investigated the clinical diagnostic value of long non-coding RNA (LncRNA) small nucleolar RNA host gene 16 (SNHG16) and explored its underlying molecular mechanism through Mycobacterium tuberculosis (M. tuberculosiinfection of macrophages. METHODS RT-qPCR analysis of the serum SNHG16 levels of the 66 healthy individuals, 67 latent TB (LTB) patients, and 67 active TB (ATB) patients. The receiver-operating characteristic (ROC) curve to detect the clinical diagnostic value of SNHG16 in TB patients. In vitro, M. tuberculosis-infected macrophages, CCK-8 and ELISA to detect cell proliferation and inflammatory factor levels. Luciferase reported assay was performed to analyze the targeting relationship between SNHG16 and miR-140-5p. RESULTS SNHG16 was significantly elevated in TB patients, and among them, ATB patients were higher than LTB patients. ROC confirmed that SNHG16 could distinguish LTB patients from healthy controls, and ATB patients from LTB patients, and can be used as a good diagnostic biomarker for TB. M. tuberculosis infection increased SNHG16 levels and promoted the proliferation and inflammation in macrophages. However, SNHG16 silencing significantly reversed the effect of infection. miR-140-5p, a direct target miRNA of SNHG16, was down-regulated in TB patients and was negatively correlated with SNHG16. When miR-140-5p was inhibited, the alleviating effect of SNHG16 silencing on M. tuberculosis infection proliferation and inflammation was significantly reversed. CONCLUSION The present results suggested that SNHG16 may be a new diagnostic biomarker for TB patients and SNHG16 silencing may alleviate TB by inhibiting the proliferation of macrophages in TB by regulation miR-140-5p.
Collapse
Affiliation(s)
- Wenna Sun
- Senior Department of Tuberculosis, The 8th Medical Center of Chinese People's Liberation Army General Hospital, Tuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Beijing 100091, China
| | - Xiushuang Zhang
- Senior Department of Tuberculosis, The 8th Medical Center of Chinese People's Liberation Army General Hospital, Tuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Beijing 100091, China
| | - Xiong He
- Senior Department of Tuberculosis, The 8th Medical Center of Chinese People's Liberation Army General Hospital, Tuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Beijing 100091, China
| | - Junxian Zhang
- Senior Department of Tuberculosis, The 8th Medical Center of Chinese People's Liberation Army General Hospital, Tuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Beijing 100091, China
| | - Xiaomeng Wang
- Senior Department of Tuberculosis, The 8th Medical Center of Chinese People's Liberation Army General Hospital, Tuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Beijing 100091, China
| | - Wen Lin
- Senior Department of Tuberculosis, The 8th Medical Center of Chinese People's Liberation Army General Hospital, Tuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Beijing 100091, China
| | - XiaoFeng Wang
- Senior Department of Tuberculosis, The 8th Medical Center of Chinese People's Liberation Army General Hospital, Tuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Beijing 100091, China
| | - Xueqiong Wu
- Senior Department of Tuberculosis, The 8th Medical Center of Chinese People's Liberation Army General Hospital, Tuberculosis Prevention and Control Key Laboratory, Beijing Key Laboratory of New Techniques of Tuberculosis Diagnosis and Treatment, Beijing 100091, China.
| |
Collapse
|
|
15
|
Ginckels P, Holvoet P. Oxidative Stress and Inflammation in Cardiovascular Diseases and Cancer: Role of Non-coding RNAs. THE YALE JOURNAL OF BIOLOGY AND MEDICINE 2022; 95:129-152. [PMID: 35370493 PMCID: PMC8961704] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
Abstract
High oxidative stress, Th1/Th17 immune response, M1 macrophage inflammation, and cell death are associated with cardiovascular diseases. Controlled oxidative stress, Th2/Treg anti-tumor immune response, M2 macrophage inflammation, and survival are associated with cancer. MiR-21 protects against cardiovascular diseases but may induce tumor growth by retaining the anti-inflammatory M2 macrophage and Treg phenotypes and inhibiting apoptosis. Down-regulation of let-7, miR-1, miR-9, miR-16, miR-20a, miR-22a, miR-23a, miR-24a, miR-26a, miR-29, miR-30a, miR-34a, miR-124, miR-128, miR-130a, miR-133, miR-140, miR-143-145, miR-150, miR-153, miR-181a, miR-378, and miR-383 may aid cancer cells to escape from stresses. Upregulation of miR-146 and miR-223 may reduce anti-tumor immune response together with miR-21 that also protects against apoptosis. MiR-155 and silencing of let-7e, miR-125, and miR-126 increase anti-tumor immune response. MiR expression depends on oxidative stress, cytokines, MYC, and TGF-β, and expression of silencing lncRNAs and circ-RNAs. However, one lncRNA or circ-RNA may have opposite effects by targeting several miRs. For example, PVT1 induces apoptosis by targeting miR-16a and miR-30a but inhibits apoptosis by silencing miR-17. In addition, levels of a non-coding RNA in a cell type depend not only on expression in that cell type but also on an exchange of microvesicles between cell types and tumors. Although we got more insight into the function of a growing number of individual non-coding RNAs, overall, we do not know enough how several of them interact in functional networks and how their expression changes at different stages of disease progression.
Collapse
Affiliation(s)
- Pieterjan Ginckels
- Department of Architecture, Brussels and Gent, KU Leuven, Leuven, Belgium
| | - Paul Holvoet
- Experimental Cardiology, KU Leuven, Leuven, Belgium,To whom all correspondence should be addressed: Paul Holvoet, Experimental
Cardiology, KU Leuven, Belgium; ; ORCID iD:
https://orcid.org/0000-0001-9201-0772
| |
Collapse
|
|
16
|
A Pleiotropic Role of Long Non-Coding RNAs in the Modulation of Wnt/β-Catenin and PI3K/Akt/mTOR Signaling Pathways in Esophageal Squamous Cell Carcinoma: Implication in Chemotherapeutic Drug Response. Curr Oncol 2022; 29:2326-2349. [PMID: 35448163 PMCID: PMC9031703 DOI: 10.3390/curroncol29040189] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2022] [Revised: 03/19/2022] [Accepted: 03/20/2022] [Indexed: 02/06/2023] Open
Abstract
Despite the availability of modern techniques for the treatment of esophageal squamous cell carcinoma (ESCC), tumor recurrence and metastasis are significant challenges in clinical management. Thus, ESCC possesses a poor prognosis and low five-year overall survival rate. Notably, the origin and recurrence of the cancer phenotype are under the control of complex cancer-related signaling pathways. In this review, we provide comprehensive knowledge about long non-coding RNAs (lncRNAs) related to Wnt/β-catenin and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway in ESCC and its implications in hindering the efficacy of chemotherapeutic drugs. We observed that a pool of lncRNAs, such as HERES, TUG1, and UCA1, associated with ESCC, directly or indirectly targets various molecules of the Wnt/β-catenin pathway and facilitates the manifestation of multiple cancer phenotypes, including proliferation, metastasis, relapse, and resistance to anticancer treatment. Additionally, several lncRNAs, such as HCP5 and PTCSC1, modulate PI3K/Akt/mTOR pathways during the ESCC pathogenesis. Furthermore, a few lncRNAs, such as AFAP1-AS1 and LINC01014, block the efficiency of chemotherapeutic drugs, including cisplatin, 5-fluorouracil, paclitaxel, and gefitinib, used for ESCC treatment. Therefore, this review may help in designing a better therapeutic strategy for ESCC patients.
Collapse
|
|
17
|
wei W, He S, Wang Z, Dong J, Xiang D, Li Y, Ren L, Kou N, Lv J. LINC01534 Promotes the Aberrant Metabolic Dysfunction and Inflammation in IL-1β-Simulated Osteoarthritic Chondrocytes by Targeting miR-140-5p. Cartilage 2021; 13:898S-907S. [PMID: 31735077 PMCID: PMC8804787 DOI: 10.1177/1947603519888787] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
OBJECTIVE Long non-coding RNA 01534 (LINC01534) is highly expressed in the tissues of patients with osteoarthritis (OA). This study investigated the mechanism of LINC01534 on abnormal metabolic dysfunction in OA chondrocytes induced by interleukin-1β (IL-1β). METHODS The quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expressions of LINC01534, aggrecan, collagen II, and matrix metalloproteinase (MMPs) in OA cartilage tissue or OA chondrocyte model induced by IL-1β. The expressions of aggrecan and collagen II in the chondrocyte were detected by Western blot. The levels of tumor necrosis factor-α (TNF-α), IL-8, IL-6, MMP-13, MMP-9, MMP-3, and prostaglandin E2 (PGE2) in chondrocyte were determined by enzyme-linked immunosorbernt assay. Bioinformatics, dual luciferin gene reporting, RNA pulldown, and Northern blot were used to determine the interaction between LINC01534 and miR-140-5p. RESULTS The results showed that LINC01534 was upregulated in both OA cartilage tissue and OA chondrocyte model. In addition, silencing LINC01534 significantly alleviated the inhibitory effect of IL-1β on expressions of aggrecan and collagen II in chondrocytes, and significantly downregulated the expression of matrix metalloproteinases in IL-1β-induced chondrocytes. Meanwhile, silencing LINC01534 also significantly inhibited the productions of proinflammatory factors NO, PGE2, TNF-α, IL-6, and IL-8 in the IL-1β-induced chondrocytes. Furthermore, miR-140-5p was confirmed to be a direct target of LINC01534. More importantly, inhibition of miR-140-5p significantly reversed the inhibitory effect of silencing LINC01534 on abnormal matrix degradation in the IL-1β-induced chondrocyte model of OA. CONCLUSION Therefore, LINC01534 could promote the abnormal matrix degradation and inflammatory response of OA chondrocytes through the targeted binding of miR-140-5p.
Collapse
Affiliation(s)
- Wei wei
- Department of Traumatology, The Second
Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province,
People’s Republic of China
| | - Shaoxuan He
- Department of Traumatology, The Second
Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province,
People’s Republic of China
| | - Zhihua Wang
- Department of Traumatology, The Second
Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province,
People’s Republic of China
| | - Junjie Dong
- Department of Traumatology, The Second
Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province,
People’s Republic of China
| | - Dong Xiang
- Department of Traumatology, The Second
Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province,
People’s Republic of China
| | - Yunxuan Li
- Department of Traumatology, The Second
Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province,
People’s Republic of China
| | - Lirong Ren
- Department of Traumatology, The Second
Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province,
People’s Republic of China
| | - Nannan Kou
- Department of Traumatology, The Second
Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province,
People’s Republic of China
| | - Jia Lv
- Department of Traumatology, The Second
Affiliated Hospital of Kunming Medical University, Kunming City, Yunnan Province,
People’s Republic of China
| |
Collapse
|
|
18
|
Ghafouri-Fard S, Khoshbakht T, Taheri M, Shojaei S. A Review on the Role of Small Nucleolar RNA Host Gene 6 Long Non-coding RNAs in the Carcinogenic Processes. Front Cell Dev Biol 2021; 9:741684. [PMID: 34671603 PMCID: PMC8522957 DOI: 10.3389/fcell.2021.741684] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 09/09/2021] [Indexed: 01/27/2023] Open
Abstract
Being located on 17q25.1, small nucleolar RNA host gene 6 (SNHG16) is a member of SNHG family of long non-coding RNAs (lncRNA) with 4 exons and 13 splice variants. This lncRNA serves as a sponge for a variety of miRNAs, namely miR-520a-3p, miR-4500, miR-146a miR-16–5p, miR-98, let-7a-5p, hsa-miR-93, miR-17-5p, miR-186, miR-302a-3p, miR-605-3p, miR-140-5p, miR-195, let-7b-5p, miR-16, miR-340, miR-1301, miR-205, miR-488, miR-1285-3p, miR-146a-5p, and miR-124-3p. This lncRNA can affect activity of TGF-β1/SMAD5, mTOR, NF-κB, Wnt, RAS/RAF/MEK/ERK and PI3K/AKT pathways. Almost all studies have reported oncogenic effect of SNHG16 in diverse cell types. Here, we explain the results of studies about the oncogenic role of SNHG16 according to three distinct sets of evidence, i.e., in vitro, animal, and clinical evidence.
Collapse
Affiliation(s)
- Soudeh Ghafouri-Fard
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Tayyebeh Khoshbakht
- Men's Health and Reproductive Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Taheri
- Skull Base Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyedpouzhia Shojaei
- Department of Critical Care Medicine, Imam Hossein Medical and Educational Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
19
|
Xu H, Ding Y, Yang X. Overexpression of Long Noncoding RNA H19 Downregulates miR-140-5p and Activates PI3K/AKT Signaling Pathway to Promote Invasion, Migration and Epithelial-Mesenchymal Transition of Ovarian Cancer Cells. BIOMED RESEARCH INTERNATIONAL 2021; 2021:6619730. [PMID: 34250088 PMCID: PMC8238588 DOI: 10.1155/2021/6619730] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 05/17/2021] [Accepted: 05/31/2021] [Indexed: 12/14/2022]
Abstract
OBJECTIVE The abnormal expression of LncRNA H19 and miR-140-5p has been linked to ovarian cancer (OC). Whether H19 directly regulates miR-140-5p in ovarian cancer cells has been unclear. In this study, we deeply explored the relationship between H19 and miR-140-5p in ovarian cancer and the mechanism of action in regulating OC progression. METHODS A total of 66 patients with OC admitted to the hospital from June 2017 to June 2019 were selected as the research group (RG), and meanwhile, 60 cases of healthy subjects were selected as the control group (CG). In addition, OC cells and normal ovarian epithelial cells were used to detect H19 and miR-140-5p expression levels and to analyze the effect of H19 on OC cells. The activation of the PI3K/AKT pathway and downstream proteins were analyzed by western blot. RESULTS H19 was highly expressed while miR-140-5p was lowly expressed in OC patients and cell lines (P < 0.050). The proliferation, invasion, migration ability, and epithelial-mesenchymal transition (EMT) of OC cells were reduced after inhibiting H19 expression, and the apoptosis rate was increased. Transfection of cells with miR-140-5p mimics brought opposite effects. Online prediction and dual-luciferase reporter (DLR) confirmed that H19 directly binds miR-140-5p. Western blot assay indicated overexpression activated the PI3K/AKT signaling pathway in OC cells. Moreover, overexpression promoted tumor growth in nude mice and was suppressed by PI3K inhibitor. CONCLUSION LncRNA H19 downregulation of miR-140-5p to activate the PI3K/AKT signaling pathway and promote the proliferation, invasion, migration and EMT of OC.
Collapse
Affiliation(s)
- Hao Xu
- Department of Traditional Chinese Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Yuan Ding
- Department of Traditional Chinese Medicine, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| | - Xiangying Yang
- ICU Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, China
| |
Collapse
|
|
20
|
Wang J, Yu PY, Yu JP, Luo JD, Sun ZQ, Sun F, Kong Z, Wang JL. KIF22 promotes progress of esophageal squamous cell carcinoma cells and is negatively regulated by miR-122. Am J Transl Res 2021; 13:4152-4166. [PMID: 34150005 PMCID: PMC8205736] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Accepted: 03/14/2021] [Indexed: 06/12/2023]
Abstract
Esophageal squamous cell carcinoma (ESCC) increases at fast rate of all cancer types in China, which urges the investigations of its potential mechanism. In this research, a highly expressed kinesin superfamily protein 22 (KIF22) was founded both in ESCC tissues and cancer cell lines. The following experiments pointed out that down-regulation of KIF22 remarkably restrained the malignant progression of ESCC cells. Besides, KIF22 knockdown promoted ESCC cells apoptosis and arrested cells in G0/G1 phase, while KIF22 also regulated the expression of cell cycle- and EMT-related proteins. Previous research revealed that the aberrant expressions of microRNAs (miRNAs) are related to tumors development. Based on the predict result, KIF22 was considered as the target of miR-122, which was demonstrated by luciferase reporter assay. miR-122 inhibitor could significantly reverse the function of KIF22 knockdown, including cell proliferation, migration and invasion. Furthermore, down-expressed miR-122 altered the function of KIF22 knockdown on cell cycle- and EMT-related proteins. In a word, this work illustrated the regulatory function of KIF22/miR-122 axis in ESSC and provided potential targets for potential targets for ESSC treatment.
Collapse
Affiliation(s)
- Jian Wang
- Department of Radiotherapy, Jiangyin People’s HospitalJiangyin 214400, Jiangsu Province, China
| | - Peng-Yi Yu
- Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow UniversityChangzhou 213003, Jiangsu Province, China
| | - Jing-Ping Yu
- Department of Radiotherapy, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical UniversityChangzhou 213003, Jiangsu Province, China
| | - Ju-Dong Luo
- Department of Radiotherapy, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical UniversityChangzhou 213003, Jiangsu Province, China
| | - Zhi-Qiang Sun
- Department of Radiotherapy, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical UniversityChangzhou 213003, Jiangsu Province, China
| | - Fei Sun
- Department of Radiotherapy, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical UniversityChangzhou 213003, Jiangsu Province, China
| | - Ze Kong
- Department of Radiotherapy, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical UniversityChangzhou 213003, Jiangsu Province, China
| | - Jian-Lin Wang
- Department of Radiotherapy, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical UniversityChangzhou 213003, Jiangsu Province, China
| |
Collapse
|
|
21
|
Biagioni A, Tavakol S, Ahmadirad N, Zahmatkeshan M, Magnelli L, Mandegary A, Samareh Fekri H, Asadi MH, Mohammadinejad R, Ahn KS. Small nucleolar RNA host genes promoting epithelial-mesenchymal transition lead cancer progression and metastasis. IUBMB Life 2021; 73:825-842. [PMID: 33938625 DOI: 10.1002/iub.2501] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 04/22/2021] [Accepted: 04/29/2021] [Indexed: 02/06/2023]
Abstract
The small nucleolar RNA host genes (SNHGs) belong to the long non-coding RNAs and are reported to be able to influence all three levels of cellular information-bearing molecules, that is, DNA, RNA, and proteins, resulting in the generation of complex phenomena. As the host genes of the small nucleolar RNAs (snoRNAs), they are commonly localized in the nucleolus, where they exert multiple regulatory functions orchestrating cellular homeostasis and differentiation as well as metastasis and chemoresistance. Indeed, worldwide literature has reported their involvement in the epithelial-mesenchymal transition (EMT) of different histotypes of cancer, being able to exploit peculiar features, for example, the possibility to act both in the nucleus and the cytoplasm. Moreover, SNHGs regulation is a fundamental topic to better understand their role in tumor progression albeit such mechanism is still debated. Here, we reviewed the biological functions of SNHGs in particular in the EMT process and discussed the perspectives for new cancer therapies.
Collapse
Affiliation(s)
- Alessio Biagioni
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", Section of Experimental Pathology and Oncology, Florence, Italy
| | - Shima Tavakol
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Nooshin Ahmadirad
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Masoumeh Zahmatkeshan
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran.,Department of Medical Nanotechnology, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Lucia Magnelli
- Department of Experimental and Clinical Biomedical Sciences "Mario Serio", Section of Experimental Pathology and Oncology, Florence, Italy
| | - Ali Mandegary
- Department of Pharmacology & Toxicology, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran
| | - Hojjat Samareh Fekri
- Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran.,Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran
| | - Malek Hossein Asadi
- Department of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran
| | - Reza Mohammadinejad
- Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran
| | - Kwang Seok Ahn
- Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea
| |
Collapse
|
|
22
|
Cheng T, Shuang W, Ye D, Zhang W, Yang Z, Fang W, Xu H, Gu M, Xu W, Guan C. SNHG16 promotes cell proliferation and inhibits cell apoptosis via regulation of the miR-1303-p/STARD9 axis in clear cell renal cell carcinoma. Cell Signal 2021; 84:110013. [PMID: 33901578 DOI: 10.1016/j.cellsig.2021.110013] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 04/20/2021] [Accepted: 04/20/2021] [Indexed: 02/06/2023]
Abstract
Clear cell renal cell carcinoma (ccRCC) is a common subtype of renal cell carcinoma (RCC) and causes many deaths. Numerous medical studies have suggested that long noncoding RNAs (lncRNAs) exert their biological functions on ccRCC. Herein, functions of lncRNA SNHG16 in ccRCC cells and the mechanism mediated by SNHG16 were investigated. The expression levels of SNHG16 and its downstream genes in ccRCC cells and RCC tissues were examined utilizing reverse transcription quantitative polymerase chain reaction analyses. Cell counting kit-8 and 5-Ethynyl-2'-deoxyuridine assays were performed to evaluate the proliferation of ccRCC cells, and flow cytometry analyses were employed to determine the apoptosis of ccRCC cells. Western blot analysis was applied to examine protein levels associated with cell proliferation and apoptosis. The combination between SNHG16 and miRNA as well as miRNA and its target gene were explored by luciferase reporter, RNA pull down, and RNA immunoprecipitation assays. The significant upregulation of SNHG16 was observed in RCC tissues and ccRCC cells. SNHG16 downregulation inhibited the proliferation and promoted the apoptosis of ccRCC cells. In addition, SNHG16 served as a competing endogenous RNA for miR-1301-3p, and STARD9 was a target gene of miR-1301-3p in ccRCC cells. SNHG16 upregulated STARD9 expression by binding with miR-1301-3p in ccRCC cells. Rescue assays validated that SNHG16 promoted ccRCC cell promotion and induced ccRCC cell apoptosis by upregulating STARD9 expression. In conclusions, SNHG16 promotes ccRCC cell proliferation and suppresses ccRCC cell apoptosis via interaction with miR-1301-3p to upregulate STARD9 expression in ccRCC cells.
Collapse
Affiliation(s)
- Tao Cheng
- Department of Urology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui, China
| | - Weibing Shuang
- Department of Urology, The First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, China
| | - Dawen Ye
- Department of Urology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui, China
| | - Wenzhi Zhang
- Innoscience Research Sdn Bhd, Subang Jaya, Malaysia
| | - Zhao Yang
- Core Facility for Protein Research, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China
| | - Wenge Fang
- Department of Urology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui, China
| | - Haibin Xu
- Department of Urology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui, China
| | - Mingli Gu
- Department of Urology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui, China
| | - Weiqiang Xu
- Department of Urology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui, China
| | - Chao Guan
- Department of Urology, The Second Affiliated Hospital of Bengbu Medical College, Bengbu 233000, Anhui, China..
| |
Collapse
|
|
23
|
Wu T, Lei MS, Gao XZ, Xiong TG, Yang K, Gong Q, Tang R, Tian YP, Fu XH. lncRNA SNHG16 Mediates Cell Proliferation and Apoptosis in Cholangiocarcinoma by Directly Targeting miR-146a-5p/GATA6 Axis. Biochem Genet 2021; 59:1311-1325. [PMID: 33797690 DOI: 10.1007/s10528-021-10059-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Accepted: 03/10/2021] [Indexed: 12/11/2022]
Abstract
Cholangiocarcinoma (CCA) is a malignant tumour with high recurrence and mortality rates and poor prognosis. However, the pathogenic mechanism remains unclear. In the present study, we aimed to investigate the roles and regulatory mechanism of SNHG16 in the occurrence and development of CCA. Gene Expression Profiling Interactive Analysis (GEPIA) was used to predict the expressions of SNHG16 and GATA6 in CCA samples from TCGA database. The levels of SNHG16, miR-146a-5p and GATA6 were evaluated using qRT-PCR. CCK-8 and flow cytometry assays were conducted to evaluate cell proliferation and apoptosis, respectively. Western blotting was applied to analyse the protein levels of GATA6 and apoptosis-related proteins. SNHG16 was significantly elevated in CCA tissues from TCGA database and CCA cell lines. Moreover, downregulation of SNHG16 restricted cell proliferation and increased apoptotic rate of RBE and HuCCT1 cells. miR-146a-5p, a downstream target of SNHG16, was shown to be an intermediate mediator of GATA6 expression regulated by SNHG16. In addition, either the miR-146a-5p inhibitor or overexpression of GATA6 obviously impaired the regulatory effects of SNHG16 downregulation in RBE and HuCCT1 cells. These data demonstrated that SNHG16 promoted cell proliferation and repressed apoptosis by regulating the miR-146a-5p/GATA6 axis, which provides some helpful insights for the diagnosis and treatment of CCA.
Collapse
Affiliation(s)
- Tao Wu
- Department of Hepatobiliary Surgery, Zhangjiajie People's Hospital, No.192 Guyong Road, Yongding District, Zhangjiajie, 427000, Hunan Province, People's Republic of China.
| | - Ming-Sheng Lei
- Department of Respiratory Medicine, Zhangjiajie People's Hospital, Zhangjiajie, 427000, Hunan Province, People's Republic of China
| | - Xu-Zhao Gao
- Department of Hepatobiliary Surgery, Zhangjiajie People's Hospital, No.192 Guyong Road, Yongding District, Zhangjiajie, 427000, Hunan Province, People's Republic of China
| | - Ting-Gang Xiong
- Department of Hepatobiliary Surgery, Zhangjiajie People's Hospital, No.192 Guyong Road, Yongding District, Zhangjiajie, 427000, Hunan Province, People's Republic of China
| | - Kang Yang
- Department of Hepatobiliary Surgery, Zhangjiajie People's Hospital, No.192 Guyong Road, Yongding District, Zhangjiajie, 427000, Hunan Province, People's Republic of China
| | - Qian Gong
- Department of Hepatobiliary Surgery, Zhangjiajie People's Hospital, No.192 Guyong Road, Yongding District, Zhangjiajie, 427000, Hunan Province, People's Republic of China
| | - Rui Tang
- Department of Hepatobiliary Surgery, Zhangjiajie People's Hospital, No.192 Guyong Road, Yongding District, Zhangjiajie, 427000, Hunan Province, People's Republic of China
| | - Yue-Peng Tian
- Department of Hepatobiliary Surgery, Zhangjiajie People's Hospital, No.192 Guyong Road, Yongding District, Zhangjiajie, 427000, Hunan Province, People's Republic of China
| | - Xiao-Hua Fu
- Department of Hepatobiliary Surgery, Zhangjiajie People's Hospital, No.192 Guyong Road, Yongding District, Zhangjiajie, 427000, Hunan Province, People's Republic of China
| |
Collapse
|
|
24
|
Bu J, Guo R, Xu XZ, Luo Y, Liu JF. LncRNA SNHG16 promotes epithelial-mesenchymal transition by upregulating ITGA6 through miR-488 inhibition in osteosarcoma. J Bone Oncol 2021; 27:100348. [PMID: 33598394 PMCID: PMC7868993 DOI: 10.1016/j.jbo.2021.100348] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 12/12/2020] [Accepted: 01/05/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Osteosarcoma is a primary cause of cancer-associated death in children and adolescents worldwide. Long non-coding RNAs SNHG16 (lncRNA SNHG16) and integrin subunit-a 6 (ITGA6) are recently reported to be involved in the tumorigenesis of osteosarcoma by multiple mechanisms. However, the correlation between SNHG16 and ITGA6 in osteosarcoma remains undetermined. METHODS Expression of miR-488, SNHG16 and ITGA6, as well as epithelial-mesenchymal transition (EMT) associated markers in osteosarcoma tissues and cell lines were examined by qRT-PCR or Western blotting. Effects of miR-488, SNHG16 and ITGA6 on cell migration, invasion were evaluated by wound-healing assay and transwell assay. Bioinformatics analysis and dual-luciferase reported assays were applied to assess the interaction among miR-488, SNHG16 and ITGA6. RNA immunoprecipitation (RIP) was also used to verify SNHG16 and miR-488 interaction. Finally, animal study was used to detect the effect of SNHG16 on osteosarcoma in vivo. RESULTS SNHG16 and ITGA6 were significantly increased while miR-488 was decreased in osteosarcoma. ITGA6 was screened as a target gene of miR-488, and SNHG16 was sponged by miR-488 in osteosarcoma cells. MiR-488 overexpression and SNHG16 knockdown suppressed migration, invasion and EMT of osteosarcoma cells. Moreover, rescue assays proved that the influences of SNHG16 on osteosarcoma cells migration, invasion and EMT were dependent on miR-488 and ITGA6. In addition, the promotive effects of SNHG16 on osteosarcoma tumor growth and metastasis were further supported by xenograft tumor growth assay. CONCLUSION SNHG16 promoted migration, invasion and EMT of osteosarcoma by sponging miR-488 to release ITGA6.
Collapse
Affiliation(s)
- Jie Bu
- Department of Orthopaedics, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan Province, People's Republic of China
| | - Ru Guo
- Department of Pediatrics, Maternal and Child Health Care Hospital of Hunan Province, Changsha 410008, Hunan Province, People's Republic of China
| | - Xue-Zheng Xu
- Department of Orthopaedics, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan Province, People's Republic of China
| | - Yi Luo
- Department of Orthopaedics, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan Province, People's Republic of China
| | - Jian-Fan Liu
- Department of Orthopaedics, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, Hunan Province, People's Republic of China
| |
Collapse
|
|
25
|
LncRNA LINC01503 aggravates the progression of cervical cancer through sponging miR-342-3p to mediate FXYD3 expression. Biosci Rep 2021; 40:224893. [PMID: 32432654 PMCID: PMC7286873 DOI: 10.1042/bsr20193371] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Revised: 04/07/2020] [Accepted: 04/20/2020] [Indexed: 12/13/2022] Open
Abstract
Cervical cancer (CC), an aggressive malignancy, has a high risk of relapse and death, mainly occurring in females. Accumulating investigations have confirmed the critical role of long noncoding RNAs (lncRNAs) in diverse cancers. LncRNA LINC01503 has been reported as an oncogene in several cancers. Nonetheless, its role and molecular mechanism in CC have not been explored. In the present study, we found that FXYD3 expression was considerably up-regulated in CC tissues and cells. Moreover, FXYD3 deficiency conspicuously hampered cell proliferation and migration while facilitated cell apoptosis in CC cells. Subsequently, molecular mechanism experiments implied that FXYD3 was a downstream target gene of miR-342-3p, and FXYD3 expression was reversely mediated by miR-342-3p. Moreover, we discovered that LINC01503 acted as the endogenous sponge for miR-342-3p. Besides, LINC01503 negatively regulated miR-342-3p expression and positively regulated FXYD3 expression in CC. Rescue assays revealed that LINC01503 depletion-induced repression on CC progression could be partly recovered by miR-342-3p inhibition, and then the co-transfection of sh-FXYD3#1 rescued this effect. Conclusively, LINC01503 aggravated CC progression through sponging miR-342-3p to mediate FXYD3 expression, providing promising therapeutic targets for CC patients.
Collapse
|
|
26
|
Hussen BM, Shoorei H, Mohaqiq M, Dinger ME, Hidayat HJ, Taheri M, Ghafouri-Fard S. The Impact of Non-coding RNAs in the Epithelial to Mesenchymal Transition. Front Mol Biosci 2021; 8:665199. [PMID: 33842553 PMCID: PMC8033041 DOI: 10.3389/fmolb.2021.665199] [Citation(s) in RCA: 20] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Accepted: 03/01/2021] [Indexed: 12/13/2022] Open
Abstract
Epithelial to mesenchymal transition (EMT) is a course of action that enables a polarized epithelial cell to undertake numerous biochemical alterations that allow it to adopt features of mesenchymal cells such as high migratory ability, invasive properties, resistance to apoptosis, and importantly higher-order formation of extracellular matrix elements. EMT has important roles in implantation and gastrulation of the embryo, inflammatory reactions and fibrosis, and transformation of cancer cells, their invasiveness and metastatic ability. Regarding the importance of EMT in the invasive progression of cancer, this process has been well studies in in this context. Non-coding RNAs (ncRNAs) have been shown to exert critical function in the regulation of cellular processes that are involved in the EMT. These processes include regulation of some transcription factors namely SNAI1 and SNAI2, ZEB1 and ZEB2, Twist, and E12/E47, modulation of chromatin configuration, alternative splicing, and protein stability and subcellular location of proteins. In the present paper, we describe the influence of ncRNAs including microRNAs and long non-coding RNAs in the EMT process and their application as biomarkers for this process and cancer progression and their potential as therapeutic targets.
Collapse
Affiliation(s)
- Bashdar Mahmud Hussen
- Pharmacognosy Department, College of Pharmacy, Hawler Medical University, Erbil, Iraq
| | - Hamed Shoorei
- Department of Anatomical Sciences, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran
| | - Mahdi Mohaqiq
- Wake Forest Institute for Regenerative Medicine, School of Medicine, Wake Forest University, Winston-Salem, NC, United States
| | - Marcel E. Dinger
- School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
| | - Hazha Jamal Hidayat
- Department of Biology, College of Education, Salahaddin University-Erbil, Erbil, Iraq
| | - Mohammad Taheri
- Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Soudeh Ghafouri-Fard
- Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
27
|
Asila A, Yang X, Kaisaer Y, Ma L. SNHG16/miR‐485‐5p/BMP7 axis modulates osteogenic differentiation of human bone marrow‐derived mesenchymal stem cells. J Gene Med 2021; 23:e3296. [PMID: 33179372 DOI: 10.1002/jgm.3296] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2020] [Revised: 11/06/2020] [Accepted: 11/06/2020] [Indexed: 01/27/2023] Open
Affiliation(s)
- Ailijiang Asila
- Department of Orthopaedics TCM Hospital of Xinjiang Xinjiang China
| | - Xinjun Yang
- Department of Orthopaedics TCM Hospital of Xinjiang Xinjiang China
| | - Yilipan Kaisaer
- Department of Orthopaedics TCM Hospital of Xinjiang Xinjiang China
| | - Lei Ma
- Department of Orthopaedics TCM Hospital of Xinjiang Xinjiang China
| |
Collapse
|
|
28
|
Liu P, Zhao L, Gu Y, Zhang M, Gao H, Meng Y. LncRNA SNHG16 promotes pulmonary fibrosis by targeting miR-455-3p to regulate the Notch2 pathway. Respir Res 2021; 22:44. [PMID: 33549106 PMCID: PMC7866661 DOI: 10.1186/s12931-021-01632-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Accepted: 01/21/2021] [Indexed: 02/06/2023] Open
Abstract
Background Idiopathic pulmonary fibrosis (IPF) is the most common interstitial lung diseases with a poor prognosis. Long non-coding RNAs (lncRNAs) have been reported to be involved in IPF in several studies. However, the role of lncRNA SNHG16 in IPF is largely unknown. Methods Firstly, experimental pulmonary fibrosis model was established by using bleomycin (BML). Histology and Western blotting assays were used to determine the different stages of fibrosis and expression of several fibrosis biomarkers. The expression of SNHG16 was detected by quantitative real-time polymerase chain reaction (qRT‐PCR). EdU staining and wound-healing assay were utilized to analyze proliferation and migration of lung fibroblast cells. Molecular mechanism of SNHG16 was explored by bioinformatics, dual-luciferase reporter assay, RNA immunoprecipitation assay (RIP), and qRT-PCR. Results The expression of SNHG16 was significantly up-regulated in bleomycin-(BLM) induced lung fibrosis and transforming growth factor-β (TGF-β)-induced fibroblast. Knockdown of SNHG16 could attenuate fibrogenesis. Mechanistically, SNHG16 was able to bind and regulate the expression of miR-455-3p. Moreover, SNHG16 also regulated the expression of Notch2 by targeting miR-455-3p. Finally, SNHG16 could promote fibrogenesis by regulating the expression of Notch2. Conclusion Taken together, our study demonstrated that SNHG16 promoted pulmonary fibrosis by targeting miR-455-3p to regulate the Notch2 pathway. These findings might provide a novel insight into pathologic process of lung fibrosis and may provide prevention strategies in the future.
Collapse
Affiliation(s)
- Panpan Liu
- Department of Pulmonary and Critical Care Medicine, Shanghai Pudong New Area Gongli Hospital, 219 Miao Pu Road, Shanghai, 200315, China
| | - Lei Zhao
- Department of Pulmonary and Critical Care Medicine, Shanghai Pudong New Area Gongli Hospital, 219 Miao Pu Road, Shanghai, 200315, China.
| | - Yuxia Gu
- Department of Pulmonary and Critical Care Medicine, Shanghai Pudong New Area Gongli Hospital, 219 Miao Pu Road, Shanghai, 200315, China
| | - Meilan Zhang
- Department of Pulmonary and Critical Care Medicine, Shanghai Pudong New Area Gongli Hospital, 219 Miao Pu Road, Shanghai, 200315, China
| | - Hongchang Gao
- Department of Pulmonary and Critical Care Medicine, Shanghai Pudong New Area Gongli Hospital, 219 Miao Pu Road, Shanghai, 200315, China
| | - Yingxia Meng
- Department of Pulmonary and Critical Care Medicine, Shanghai Pudong New Area Gongli Hospital, 219 Miao Pu Road, Shanghai, 200315, China
| |
Collapse
|
|
29
|
Comprehensive Analysis of lncRNAs Related to the Prognosis of Esophageal Cancer Based on ceRNA Network and Cox Regression Model. BIOMED RESEARCH INTERNATIONAL 2021; 2020:3075729. [PMID: 33381546 PMCID: PMC7748909 DOI: 10.1155/2020/3075729] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/14/2020] [Revised: 11/15/2020] [Accepted: 11/21/2020] [Indexed: 01/10/2023]
Abstract
Background Esophageal cancer is one of the most deadly malignant tumors. Among the common malignant tumors in the world, esophageal cancer is ranked seventh, which has a high mortality rate. Long noncoding RNAs (lncRNAs) play an important role in the occurrence and development of various tumors. lncRNAs can competitively bind microRNAs (miRNAs) with mRNA, which can regulate the expression level of the encoded gene at the posttranscriptional level. This regulatory mechanism is called the competitive endogenous RNA (ceRNA) hypothesis, and ceRNA has important research value in tumor-related research. However, the regulation of lncRNAs is less studied in the study of esophageal cancer. Methods The Cancer Genome Atlas (TCGA) database was used to download transcriptome profiling data of esophageal cancer. Gene expression quantification data contains 160 cancer samples and 11 normal samples. These data were used to identify differentially expressed lncRNAs and mRNAs. miRNA expression data includes 185 cancer samples and 13 normal samples. The differentially expressed RNAs were identified using the edgeR package in R software. Then, the miRcode database was used to predict miRNAs that bind to lncRNAs. MiRTarBase, miRDB, and TargetScan databases were used to predict the target genes of miRNAs. Cytoscape software was used to draw ceRNA network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using DAVID 6.8. Finally, multifactor cox regression was used to screen lncRNAs related to prognosis. Results We have screened 1331 DElncRNAs, 3193 DEmRNAs, and 162 DEmiRNAs. Among them, the ceRNA network contains 111 lncRNAs, 11 miRNAs, and 63 DEmRNAs. Finally, we established a prediction model containing three lncRNAs through multifactor Cox regression analysis. Conclusions Our research screened out three independent prognostic lncRNAs from the ceRNA network and constructed a risk assessment model. This is helpful to understand the regulatory role of lncRNAs in esophageal cancer.
Collapse
|
|
30
|
Huang L, Ding Y, Yang L, Jiang X, Xia Z, You Z. The effect of LncRNA SNHG16 on vascular smooth muscle cells in CHD by targeting miRNA-218-5p. Exp Mol Pathol 2020; 118:104595. [PMID: 33359036 DOI: 10.1016/j.yexmp.2020.104595] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Revised: 12/09/2020] [Accepted: 12/09/2020] [Indexed: 01/21/2023]
Abstract
PURPOSE To explore the role of SNHG16 in coronary heart disease (CHD) and its effect on vascular smooth muscle cells via miR-218-5p. METHODS A quantitative real time polymerase chain reaction (qRT-PCR) assay was carried out to determine the expression of serum SNHG16 and miR-218-5p in the observation group before and after treatment and in the control group. Then, receiver operating characteristic (ROC) curves were drawn to analyze the value of SNHG16 and miR-218-5p in the diagnosis and prognosis prediction of CHD. Furthermore, purchased coronary artery smooth muscle cells (HCASMC) were transfected with SNHG16 mimics, SNHG16 inhibitor, miR-218-5p mimics, miR-218-5p inhibitor, or negative control, and then the cell proliferation, migration, apoptosis, and apoptosis-related proteins (Bax, Bcl-2, and Caspase-3) and Wnt/β-catenin signaling pathway-related proteins (c-myc and β-catenin) in the cells were detected. RESULTS Both SNHG16 and miR-218-5 had good predictive value for the development and recurrence of CHD (P < 0.001). In addition, cell experiments showed that inhibition of SNHG16 weakened the proliferation and migration of HCASMC cells and intensified their apoptosis, SNHG16 and miR-218-5p had the same binding sites, and the dual luciferase reporter assay revealed that the fluorescence activity of HG16-WT was inhibited by transfected miR-mimics, but enhanced by transfected miR-inhibitor (both P < 0.050). Furthermore, the rescue experiment revealed that the effect of inhibiting SNHG16 on HCASMC cells was completely reversed by miR-218-5p (P > 0.050). CONCLUSIONS Highly expressed SNHG16 targetedly regulates miR-218-5p and promotes the proliferation and migration of HCASMC via the Wnt/β-catenin signaling pathway, giving rise to CHD.
Collapse
Affiliation(s)
- Lin Huang
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of NanChang University, Nanchang 330006, Jiangxi Province, China
| | - Ying Ding
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of NanChang University, Nanchang 330006, Jiangxi Province, China
| | - Lu Yang
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of NanChang University, Nanchang 330006, Jiangxi Province, China
| | - Xinghua Jiang
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of NanChang University, Nanchang 330006, Jiangxi Province, China
| | - Zhen Xia
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of NanChang University, Nanchang 330006, Jiangxi Province, China
| | - Zhigang You
- Department of Cardiovascular Medicine, The Second Affiliated Hospital of NanChang University, Nanchang 330006, Jiangxi Province, China.
| |
Collapse
|
|
31
|
Lavery A, Turkington RC. Transcriptomic biomarkers for predicting response to neoadjuvant treatment in oesophageal cancer. Gastroenterol Rep (Oxf) 2020; 8:411-424. [PMID: 33442473 PMCID: PMC7793050 DOI: 10.1093/gastro/goaa065] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 04/21/2020] [Accepted: 07/15/2020] [Indexed: 02/07/2023] Open
Abstract
Oesophageal cancer is a devastating disease with poor outcomes and is the sixth leading cause of cancer death worldwide. In the setting of resectable disease, there is clear evidence that neoadjuvant chemotherapy and chemoradiotherapy result in improved survival. Disappointingly, only 15%-30% of patients obtain a histopathological response to neoadjuvant therapy, often at the expense of significant toxicity. There are no predictive biomarkers in routine clinical use in this setting and the ability to stratify patients for treatment could dramatically improve outcomes. In this review, we aim to outline current progress in evaluating predictive transcriptomic biomarkers for neoadjuvant therapy in oesophageal cancer and discuss the challenges facing biomarker development in this setting. We place these issues in the wider context of recommendations for biomarker development and reporting. The majority of studies focus on messenger RNA (mRNA) and microRNA (miRNA) biomarkers. These studies report a range of different genes involved in a wide variety of pathways and biological processes, and this is explained to a large extent by the different platforms and analysis methods used. Many studies are also vastly underpowered so are not suitable for identifying a candidate biomarker. Multiple molecular subtypes of oesophageal cancer have been proposed, although little is known about how these relate to clinical outcomes. We anticipate that the accumulating wealth of genomic and transcriptomic data and clinical trial collaborations in the coming years will provide unique opportunities to stratify patients in this poor-prognosis disease and recommend that future biomarker development incorporates well-designed retrospective and prospective analyses.
Collapse
Affiliation(s)
- Anita Lavery
- Patrick G Johnston Centre for Cancer Research, Queen’s University Belfast, Belfast, UK
| | - Richard C Turkington
- Patrick G Johnston Centre for Cancer Research, Queen’s University Belfast, Belfast, UK
| |
Collapse
|
|
32
|
Cai RD, Zhang CC, Xie LL, Wang PC, Huang CX, Chen JL, Lv HT. SNHG1 Promotes Malignant Progression of Glioma by Targeting miR-140-5p and Regulating PI3K/AKT Pathway. Cancer Manag Res 2020; 12:12011-12020. [PMID: 33262651 PMCID: PMC7700088 DOI: 10.2147/cmar.s269572] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Accepted: 10/15/2020] [Indexed: 12/19/2022] Open
Abstract
PURPOSE To explore the regulatory mechanism of long non-coding RNA small nucleolar RNA host gene 1 (SNHG1) in glioma. MATERIALS AND METHODS The expression of SNHG1 and miR-140-5p in glioma tissues and glioma cell lines (LN-18, KNS-81, and KALS-1) was determined, and the effect of the two on cell proliferation, invasion, and PI3K/AKT pathway was analyzed. RESULTS SNHG1 was overexpressed in glioma tissues, while miR-140-5p was underexpressed in them, and there was a significant negative correlation between SNHG1 and miR-140-5p. In addition, both down-regulation of SNHG1 and up-regulation of miR-140-5p significantly inhibited the malignant proliferation and invasion of glioma, intensified the apoptosis, and also significantly suppressed the activation of the PI3K/AKT pathway. The dual-luciferase reporter assay, RNA pull-down assay, and RIP determination all confirmed that there was a targeting relationship between SNHG1 and miR-140-5p, and there was no difference between KNS-81 and KALS-1 cells transfected with SNHG1+mimics and si-SNHG1+inhibitor and those in the si-NC group with unrelated sequences in terms of cell malignant progression. CONCLUSION SNHG1/miR-140-5p axis and its regulation on PI3K/AKT pathway might be a novel therapeutic direction to curb the malignant progression of glioma.
Collapse
Affiliation(s)
- Ren-Duan Cai
- Department of Neurosurgery, Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, People’s Republic of China
| | - Chao-Cai Zhang
- Department of Neurosurgery, Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University, Haikou, Hainan Province, People’s Republic of China
| | - Li-Li Xie
- Department of Neurology, Dalian Central Hospital, Dalian, Liaoning Province, People’s Republic of China
| | - Peng-Cheng Wang
- Department of Neurosurgery, Hainan People’s Hospital, Haikou, Hainan Province, People's Republic of China
| | - Chui-Xue Huang
- Department of Neurosurgery, Hainan People’s Hospital, Haikou, Hainan Province, People's Republic of China
| | - Jian-Long Chen
- Department of Neurosurgery, Hainan People’s Hospital, Haikou, Hainan Province, People's Republic of China
| | - Hong-Tao Lv
- Department of Neurosurgery, The First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning Province, People’s Republic of China
| |
Collapse
|
|
33
|
Construction and Analysis of lncRNA-Mediated ceRNA Network in Nasopharyngeal Carcinoma Based on Weighted Correlation Network Analysis. BIOMED RESEARCH INTERNATIONAL 2020; 2020:1468980. [PMID: 33102573 PMCID: PMC7569441 DOI: 10.1155/2020/1468980] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 09/12/2020] [Accepted: 09/25/2020] [Indexed: 12/24/2022]
Abstract
Increasing evidence indicated that aberrant expression of long noncoding RNAs (lncRNAs) are involved in tumorigenesis of nasopharyngeal carcinoma (NPC). The purpose of this study was to construct a lncRNA-mediated ceRNA network based on weighted correlation network analysis (WGCNA). First, modules with highly correlated genes were identified from GSE102349 via WGCNA, and the preservation of the modules was evaluated by GSE68799. Then, the differentially expressed lncRNAs and mRNAs identified from GSE12452 which belonged to the same WGCNA modules and the differentially expressed miRNAs identified from GSE32960 were used to construct a ceRNA network. The prognostic value of the network was evaluated by survival analysis. Furthermore, a risk score model for predicting progression-free survival (PFS) of NPC patients was established via LASSO-penalized Cox regression, and the differences in the expression of the lncRNAs between high- and low-risk groups were investigated. Finally, 14 stable modules were identified, and a ceRNA network composed of 11 lncRNAs, 15 miRNAs, and 40 mRNAs was established. The lncRNAs and mRNAs in the network belonged to the turquoise and salmon modules. Survival analysis indicated that ZNF667-AS1, LDHA, LMNB2, TPI1, UNG, and hsa-miR-142-3p were significantly correlated with the prognosis of NPC. Gene set enrichment analysis indicated that the upregulation of ZNF667-AS1 was associated with some immune-related pathways. Besides, a risk score model consisting of 12 genes was constructed and showed a good performance in predicting PFS for NPC patients. Among the 11 lncRNAs in the ceRNA network, SNHG16, SNHG17, and THAP9-AS1 were upregulated in the high-risk group of NPC, while ZNF667-AS1 was downregulated in the high-risk group of NPC. These results will promote our understanding of the crosstalk among lncRNAs, miRNAs, and mRNAs in the tumorigenesis and progression of NPC.
Collapse
|
|
34
|
Xiao Y, Xiao T, Ou W, Wu Z, Wu J, Tang J, Tian B, Zhou Y, Su M, Wang W. LncRNA SNHG16 as a potential biomarker and therapeutic target in human cancers. Biomark Res 2020; 8:41. [PMID: 32944244 PMCID: PMC7487997 DOI: 10.1186/s40364-020-00221-4] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2020] [Accepted: 08/26/2020] [Indexed: 01/27/2023] Open
Abstract
Long non-coding RNAs (lncRNAs) represent an important class of RNAs comprising more than 200 nucleotides, which are produced by RNA polymerase II. Although lacking an open reading framework and protein-encoding activity, lncRNAs can mediate endogenous gene expression by serving as chromatin remodeler, transcriptional or post-transcriptional modulator, and splicing regulator during gene modification. In recent years, increasing evidence shows the significance of lncRNAs in many malignancies, with vital roles in tumorigenesis and cancer progression. Moreover, lncRNAs were also considered potential diagnostic and prognostic markers in cancer. The lncRNA small nuclear RNA host gene 16 (SNHG16), found on chromosome 17q25.1, represents a novel tumor-associated lncRNA. SNHG16 was recently found to exhibit dysregulated expression in a variety of malignancies. There are growing evidence of SNHG16's involvement in characteristics of cancer, including proliferation, apoptosis, together with its involvement in chemoresistance. In addition, SNHG16 has been described as a promising diagnostic and prognostic biomarker in cancer patients. The current review briefly summarizes recently reported findings about SNHG16 and discuss its expression, roles, mechanisms, and diagnostic and prognostic values in human cancers.
Collapse
Affiliation(s)
- Yuhang Xiao
- Thoracic Surgery Department 2, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013 PR China
- Department of Pharmacy, Xiangya Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410001 PR China
| | - Ta Xiao
- Institute of Dermatology, Chinese Academy of Medical Sciences & Peking Union Medical College, Nanjing, Jiangsu 210042 China
| | - Wei Ou
- Department of Pharmacy, The First People’s Hospital of Yue Yang, Yue Yang, PR China
| | - Zhining Wu
- Thoracic Surgery Department 2, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013 PR China
| | - Jie Wu
- Thoracic Surgery Department 2, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013 PR China
| | - Jinming Tang
- Thoracic Surgery Department 2, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013 PR China
| | - Bo Tian
- Thoracic Surgery Department 2, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013 PR China
| | - Yong Zhou
- Thoracic Surgery Department 2, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013 PR China
| | - Min Su
- Thoracic Surgery Department 2, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013 PR China
- Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| | - Wenxiang Wang
- Thoracic Surgery Department 2, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013 PR China
- Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China
| |
Collapse
|
|
35
|
de Morais EF, Rolim LSA, de Melo Fernandes Almeida DR, de Farias Morais HG, de Souza LB, de Almeida Freitas R. Biological role of epithelial-mesenchymal-transition-inducing transcription factors in head and neck squamous cell carcinoma: A systematic review. Arch Oral Biol 2020; 119:104904. [PMID: 32947165 DOI: 10.1016/j.archoralbio.2020.104904] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2020] [Revised: 09/01/2020] [Accepted: 09/02/2020] [Indexed: 02/06/2023]
Abstract
OBJECTIVE The aim of this systematic review was to explore the biological functions and mechanisms of epithelial-mesenchymal transition-inducing transcription factors in head and neck squamous cell carcinoma-derived cell lines. In addition, we analyzed the possible usefulness of epithelial-mesenchymal transition-inducing transcription factors as a future therapeutic target. DESIGN An electronic search was performed in EMBASE, Medline/PubMed, Chinese BioMedical Literature Databases, and Cochrane Collaboration Library. Articles evaluating the relationship between epithelial-mesenchymal transition-inducing transcription factors and the biological behavior of head and neck squamous cell carcinoma cell lines were selected for this systematic review. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. RESULTS After application of the previously established inclusion/exclusion criteria, 23 articles were included in the qualitative synthesis. Our study showed that epithelial-mesenchymal transition-inducing transcription factors are essential components during the progression of head and neck squamous cell carcinomas and their overexpression is associated with a greater capacity of dissemination and survival of the tumor and resistance to cancer treatment. The inhibition of epithelial-mesenchymal transition-inducing transcription factors is able to reverse the epithelial-mesenchymal transition process and to increase the sensitivity of head and neck squamous cell carcinoma cell lines to radio/chemotherapy. CONCLUSIONS Analysis of the expression of epithelial-mesenchymal transition-inducing transcription factors for the prediction of prognosis and response to cancer treatment may have a significant clinical impact.
Collapse
|
|
36
|
Chen ZY, Wang XY, Yang YM, Wu MH, Yang L, Jiang DT, Cai H, Peng Y. LncRNA SNHG16 promotes colorectal cancer cell proliferation, migration, and epithelial–mesenchymal transition through miR-124-3p/MCP-1. Gene Ther 2020; 29:193-205. [DOI: 10.1038/s41434-020-0176-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2019] [Revised: 04/20/2020] [Accepted: 07/07/2020] [Indexed: 12/25/2022]
|
|
37
|
Yang S, Li X, Shen W, Hu H, Li C, Han G. MicroRNA-140 Represses Esophageal Cancer Progression via Targeting ZEB2 to Regulate Wnt/β-Catenin Pathway. J Surg Res 2020; 257:267-277. [PMID: 32862055 DOI: 10.1016/j.jss.2020.07.074] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Revised: 06/11/2020] [Accepted: 07/11/2020] [Indexed: 01/18/2023]
Abstract
BACKGROUND MicroRNAs have been reported to play regulatory functions in various cancers, including esophageal cancer. The aim of this study was to investigate the effects of miR-140 on the progression of esophageal cancer and the underlying regulatory mechanism. METHODS The levels of miR-140 and zinc finger E-box-binding homeobox 2 (ZEB2) messenger RNA in esophageal cancer tissues and cell lines were measured by quantitative real-time polymerase chain reaction. The protein levels of ZEB2, β-catenin, c-Myc, and cyclinD1 were determined by Western blot. Cell proliferation and apoptosis were determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay and flow cytometry, respectively. Cell migration and invasion were assessed by transwell assay. In addition, the relationship between miR-140 and ZEB2 was predicted by TargetScan online database and confirmed by dual-luciferase reporter assay. The tumor xenograft model was used to verify the role of miR-140 in esophageal cancer progression in vivo. RESULTS The expression of miR-140 was downregulated whereas ZEB2 expression was upregulated in esophageal cancer tissues compared with paracancerous normal tissues. Functionally, both miR-140 overexpression and ZEB2 knockdown inhibited proliferation, migration, and invasion and induced apoptosis in esophageal cancer cells. ZEB2 overexpression reversed the effects of miR-140 on proliferation, apoptosis, migration, and invasion of esophageal cancer cells. Mechanistically, ZEB2 was identified as a target of miR-140. Furthermore, miR-140 suppressed Wnt/β-catenin pathway by regulating ZEB2 expression in esophageal cancer cells. MiR-140 inhibited tumor growth of esophageal cancer through repressing ZEB2 expression in vivo. CONCLUSIONS Our results demonstrated that miR-140 inhibited esophageal cancer development by targeting ZEB2 through inactivating Wnt/β-catenin pathway.
Collapse
Affiliation(s)
- Song Yang
- Department of Oncology, Taizhou People's Hospital, Taizhou, Jiangsu, China
| | - Xiangyi Li
- Department of Endocrinology, Taizhou People's Hospital, Taizhou, Jiangsu, China
| | - Wenhao Shen
- Department of Oncology, Taizhou People's Hospital, Taizhou, Jiangsu, China
| | - Haitao Hu
- Clinical Laboratory, Taizhou People's Hospital, Taizhou, Jiangsu, China
| | - Chen Li
- Department of Stomatology, Taizhou People's Hospital, Taizhou, Jiangsu, China
| | - Gaohua Han
- Department of Oncology, Taizhou People's Hospital, Taizhou, Jiangsu, China.
| |
Collapse
|
|
38
|
Liu W, Liu P, Gao H, Wang X, Yan M. Long non-coding RNA PGM5-AS1 promotes epithelial-mesenchymal transition, invasion and metastasis of osteosarcoma cells by impairing miR-140-5p-mediated FBN1 inhibition. Mol Oncol 2020; 14:2660-2677. [PMID: 32412676 PMCID: PMC7530781 DOI: 10.1002/1878-0261.12711] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Revised: 04/14/2020] [Accepted: 05/11/2020] [Indexed: 01/31/2023] Open
Abstract
Osteosarcoma is an uncommon tumor occurring in bone, accompanied by elevated incidence and reduced rate of healing. Epithelial‐to‐mesenchymal transition (EMT) serves as a conceptual paradigm to explain the invasion and metastasis of osteosarcoma and other cancers. Hence, developing effective therapeutic strategy to treat the EMT of osteosarcoma is essential. Here, we identified the molecular mechanism of long noncoding RNA (lncRNA) PGM5‐AS1 in EMT and progression of osteosarcoma. Microarray‐based analysis was employed to screen the osteosarcoma‐related differentially expressed lncRNAs. The levels of PGM5‐AS1 as well as microRNA‐140‐5p (miR‐140‐5p) and fibrillin‐1 (FBN1) in osteosarcoma tissues and cells were determined. Dual‐luciferase reporter gene assay, RNA pull‐down assay, and RNA immunoprecipitation assay were conducted to validate the relationship among PGM5‐AS1, miR‐140‐5p, and FBN1. Expression of PGM5‐AS1, miR‐140‐5p, and FBN1 was altered by overexpression, shRNA, mimic, or inhibitors in order to investigate how they regulated migration, invasion, and EMT of osteosarcoma cells in vitro. Loss‐ and gain‐of‐function approaches were employed in nude mice to detect their roles in tumorigenesis in vivo. Osteosarcoma tissues and cells exhibited low expression of miR‐140‐5p, but high expression of PGM5‐AS1 and FBN1. PGM5‐AS1 competitively bound to miR‐140‐5p to upregulate FBN1. Furthermore, hindering PGM5‐AS1 and FBN1 or overexpressing miR‐140‐5p dampened migration, invasion, and EMT of osteosarcoma cells in vitro. Furthermore, silencing PGM5‐AS1 or FBN1, or overexpressing miR‐140‐5p markedly inhibited tumorigenesis in nude mice in vivo. Taken together, PGM5‐AS1 depletion causes FBN1 reduction to retard osteosarcoma processes by negatively modulating miR‐140‐5p.
Collapse
Affiliation(s)
- Wei Liu
- Department of Spine Surgery, The First Hospital of Jilin University, Changchun, China
| | - Pengcheng Liu
- Department of Hand and Foot Surgery, The First Hospital of Jilin University, Changchun, China
| | - Hang Gao
- Department of Bone and Joint Surgery, The First Hospital of Jilin University, Changchun, China
| | - Xu Wang
- Department of Colorectal and Anal Surgery, The First Hospital of Jilin University, Changchun, China
| | - Ming Yan
- Department of Spine Surgery, The First Hospital of Jilin University, Changchun, China
| |
Collapse
|
|
39
|
Teng H, Li M, Qian L, Yang H, Pang M. Long non‑coding RNA SNHG16 inhibits the oxygen‑glucose deprivation and reoxygenation‑induced apoptosis in human brain microvascular endothelial cells by regulating miR‑15a‑5p/bcl‑2. Mol Med Rep 2020; 22:2685-2694. [PMID: 32945414 PMCID: PMC7453539 DOI: 10.3892/mmr.2020.11385] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2019] [Accepted: 06/03/2020] [Indexed: 12/20/2022] Open
Abstract
MicroRNA (miR) 15a-5p can promote ischemia/reperfusion (I/R)-induced apoptosis of cerebral vascular endothelial cells, which is inhibited by long non-coding RNAs (lncRNAs). The present study investigated the potential of lncRNAs targeting miR-15a-5p to regulate oxygen-glucose deprivation and reoxygenation (OGD-R)-induced apoptosis of human brain microvascular endothelial cells (hBMECs). hBMECs were transfected with or without miR-15a-5p or its mutant, together with p-small nucleolar RNA host gene 16 (SNHG16) or its mutant. Following OGD-R, proliferation, apoptosis and miR-15a-5p, SNHG16 and Bcl-2 expression levels were determined using MTT, flow cytometry, reverse transcription-quantitative PCR or western blotting. The potential interaction of SNHG16 with miR-15a-5p was analyzed by pull-down, luciferase and immunoprecipitation assays. OGD-R induced apoptosis of hBMECs and increased miR-15a-5p expression levels in a time-dependent manner. miR-15a-5p overexpression decreased the proliferation of hBMECs and promoted apoptosis by decreasing Bcl-2 expression levels. SNHG16 was pulled-down by miR-15a-5p and anti-Ago2. miR-15a-5p overexpression significantly decreased SNHG16-regulated luciferase activity and hBMEC survival by increasing apoptosis. SNHG16 overexpression decreased miR-15a-5p expression levels in hBMECs. SNHG16 gradually decreased following OGD-R and its overexpression decreased miR-15a-5p expression levels and promoted the proliferation of hBMECs by decreasing apoptosis. SNHG16 enhanced Bcl-2 expression levels in hBMECs, which was abrogated by miR-15a-5p. Bioinformatics suggest that SNHG16 may antagonize the binding of miR-15a-5p to the 3′UTR of Bcl-2 mRNA. These findings suggest that SNHG16 may protect hBMECs from OGD-R-induced apoptosis by antagonizing the miR-15a-5p/bcl-2 axis. Thus, targeting SNHG16-based mechanisms may provide novel therapeutic strategies for treatment of ischemic stroke.
Collapse
Affiliation(s)
- Hongwei Teng
- Department of Neurosurgery, Binhai County People's Hospital, Yancheng, Jiangsu 224500, P.R. China
| | - Ming Li
- Department of Laboratory Medicine, Binhai County People's Hospital, Yancheng, Jiangsu 224500, P.R. China
| | - Lei Qian
- Department of Laboratory Medicine, Binhai County People's Hospital, Yancheng, Jiangsu 224500, P.R. China
| | - Hua Yang
- Department of Neurosurgery, Binhai County People's Hospital, Yancheng, Jiangsu 224500, P.R. China
| | - Mingzhi Pang
- Department of Neurosurgery, Wuxi No. 2 Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu 214002, P.R. China
| |
Collapse
|
|
40
|
MicroRNAs and Their Influence on the ZEB Family: Mechanistic Aspects and Therapeutic Applications in Cancer Therapy. Biomolecules 2020; 10:biom10071040. [PMID: 32664703 PMCID: PMC7407563 DOI: 10.3390/biom10071040] [Citation(s) in RCA: 56] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2020] [Revised: 07/06/2020] [Accepted: 07/10/2020] [Indexed: 02/07/2023] Open
Abstract
Molecular signaling pathways involved in cancer have been intensively studied due to their crucial role in cancer cell growth and dissemination. Among them, zinc finger E-box binding homeobox-1 (ZEB1) and -2 (ZEB2) are molecules that play vital roles in signaling pathways to ensure the survival of tumor cells, particularly through enhancing cell proliferation, promoting cell migration and invasion, and triggering drug resistance. Importantly, ZEB proteins are regulated by microRNAs (miRs). In this review, we demonstrate the impact that miRs have on cancer therapy, through their targeting of ZEB proteins. MiRs are able to act as onco-suppressor factors and inhibit the malignancy of tumor cells through ZEB1/2 down-regulation. This can lead to an inhibition of epithelial-mesenchymal transition (EMT) mechanism, therefore reducing metastasis. Additionally, miRs are able to inhibit ZEB1/2-mediated drug resistance and immunosuppression. Additionally, we explore the upstream modulators of miRs such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), as these regulators can influence the inhibitory effect of miRs on ZEB proteins and cancer progression.
Collapse
|
|
41
|
Ghafouri‐Fard S, Shoorei H, Dashti S, Branicki W, Taheri M. Expression profile of lncRNAs and miRNAs in esophageal cancer: Implications in diagnosis, prognosis, and therapeutic response. J Cell Physiol 2020; 235:9269-9290. [DOI: 10.1002/jcp.29825] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2020] [Revised: 05/11/2020] [Accepted: 05/18/2020] [Indexed: 12/24/2022]
Affiliation(s)
- Soudeh Ghafouri‐Fard
- Department of Medical Genetics Shahid Beheshti University of Medical Sciences Tehran Iran
| | - Hamed Shoorei
- Department of Anatomical Sciences Birjand University of Medical Sciences Birjand Iran
| | - Sepideh Dashti
- Department of Medical Genetics Shahid Beheshti University of Medical Sciences Tehran Iran
| | - Wojciech Branicki
- Malopolska Centre of Biotechnology, Jagiellonian University Kraków Poland
| | - Mohammad Taheri
- Urogenital Stem Cell Research Center, Shahid Beheshti University of Medical Sciences Tehran Iran
| |
Collapse
|
|
42
|
Zhao H, Shi J, Zhang Y, Xie A, Yu L, Zhang C, Lei J, Xu H, Leng Z, Li T, Huang W, Lin S, Wang L, Xiao Y, Li X. LncTarD: a manually-curated database of experimentally-supported functional lncRNA-target regulations in human diseases. Nucleic Acids Res 2020; 48:D118-D126. [PMID: 31713618 PMCID: PMC7145524 DOI: 10.1093/nar/gkz985] [Citation(s) in RCA: 53] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Revised: 10/12/2019] [Accepted: 10/16/2019] [Indexed: 12/11/2022] Open
Abstract
Long non-coding RNAs (lncRNAs) are associated with human diseases. Although lncRNA–disease associations have received significant attention, no online repository is available to collect lncRNA-mediated regulatory mechanisms, key downstream targets, and important biological functions driven by disease-related lncRNAs in human diseases. We thus developed LncTarD (http://biocc.hrbmu.edu.cn/LncTarD/ or http://bio-bigdata.hrbmu.edu.cn/LncTarD), a manually-curated database that provides a comprehensive resource of key lncRNA–target regulations, lncRNA-influenced functions, and lncRNA-mediated regulatory mechanisms in human diseases. LncTarD offers (i) 2822 key lncRNA–target regulations involving 475 lncRNAs and 1039 targets associated with 177 human diseases; (ii) 1613 experimentally-supported functional regulations and 1209 expression associations in human diseases; (iii) important biological functions driven by disease-related lncRNAs in human diseases; (iv) lncRNA–target regulations responsible for drug resistance or sensitivity in human diseases and (v) lncRNA microarray, lncRNA sequence data and transcriptome data of an 11 373 pan-cancer patient cohort from TCGA to help characterize the functional dynamics of these lncRNA–target regulations. LncTarD also provides a user-friendly interface to conveniently browse, search, and download data. LncTarD will be a useful resource platform for the further understanding of functions and molecular mechanisms of lncRNA deregulation in human disease, which will help to identify novel and sensitive biomarkers and therapeutic targets.
Collapse
Affiliation(s)
- Hongying Zhao
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China
| | - Jian Shi
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China
| | - Yunpeng Zhang
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China
| | - Aimin Xie
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China
| | - Lei Yu
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China
| | - Caiyu Zhang
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China
| | - Junjie Lei
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China
| | - Haotian Xu
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China
| | - Zhijun Leng
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China
| | - Tengyue Li
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China
| | - Waidong Huang
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China
| | - Shihua Lin
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China
| | - Li Wang
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China
| | - Yun Xiao
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China
| | - Xia Li
- College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China.,College of Bioinformatics, Hainan Medical University, Haikou 570100, China
| |
Collapse
|
|
43
|
Pan H, Zhao F, Yang Y, Chang N. Overexpression of long non-coding RNA SNHG16 against cerebral ischemia-reperfusion injury through miR-106b-5p/LIMK1 axis. Life Sci 2020; 254:117778. [PMID: 32407850 DOI: 10.1016/j.lfs.2020.117778] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Revised: 04/19/2020] [Accepted: 05/09/2020] [Indexed: 11/18/2022]
Abstract
Long non-coding RNA (LncRNA) involved in types of physiological insults and diseases via regulating the responses of complex molecular, including cerebral ischemia-reperfusion (I/R) injury. LncRNA SNHG16 played a potential role in ketamine-induced neurotoxicity. In this study, we utilized an in vitro cell model of I/R to examine the specific function and mechanism of LncRNA SNHG16 in oxygen-glucose deprivation and reperfusion (OGD/R) induced SH-SY5Y cells. After in vitro treatment of OGD/R, the lower the SH-SY5Y cell survival, the higher cell the apoptosis and increased caspase-3 activity was observed. Also, OGD/R induced endoplasmic reticulum stress (ERS) through increasing GRP78 and CHOP expressions and down-regulated LncRNA SNHG16 in SH-SY5Y cells. Conversely, LncRNA SNHG16 overexpression promoted OGD/R induced SH-SY5Y cell survival, suppressed its apoptosis, and caspase-3 activity. GRP78 and CHOP expressions were significantly suppressed in LncRNA SNHG16 overexpressing cells. MiR-106b-5p expression was increased and LIMK1 expression was down-regulated in OGD/R induced SH-SY5Y cells, and these effects were reversed by LncRNA SNHG16 overexpression, respectively. Moreover, LIMK1 is a direct target of MiR-106b-5p, and knockdown of LIMK1 reversed the effects of LncRNA SNHG16 on OGD/R-induced SH-SY5Y cells biology. Altogether, these results confirmed an important neuroprotection role of LncRNA SNHG16 in OGD/R induced SH-SY5Y cells injury, and miR-106b-5p/LIMK1 signal axis was involved in the action of LncRNA SNHG16.
Collapse
Affiliation(s)
- Haojun Pan
- Department of Neurology, Huaihe Hospital of Henan University, Kaifeng 475000, Henan province, China
| | - Fangfang Zhao
- Department of Neurology, Huaihe Hospital of Henan University, Kaifeng 475000, Henan province, China
| | - Yanmin Yang
- Department of Neurology, Huaihe Hospital of Henan University, Kaifeng 475000, Henan province, China
| | - Na Chang
- Department of Neurology, Huaihe Hospital of Henan University, Kaifeng 475000, Henan province, China..
| |
Collapse
|
|
44
|
Zimta AA, Tigu AB, Braicu C, Stefan C, Ionescu C, Berindan-Neagoe I. An Emerging Class of Long Non-coding RNA With Oncogenic Role Arises From the snoRNA Host Genes. Front Oncol 2020; 10:389. [PMID: 32318335 PMCID: PMC7154078 DOI: 10.3389/fonc.2020.00389] [Citation(s) in RCA: 100] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Accepted: 03/04/2020] [Indexed: 12/24/2022] Open
Abstract
The small nucleolar RNA host genes (SNHGs) are a group of long non-coding RNAs, which are reported in many studies as being overexpressed in various cancers. With very few exceptions, the SNHGs (SNHG1, SNHG3, SNHG5, SNHG6, SNHG7, SNHG12, SNHG15, SNHG16, SNHG20) are recognized as inducing increased proliferation, cell cycle progression, invasion, and metastasis of cancer cells, which makes this class of transcripts a viable biomarker for cancer development and aggressiveness. Through our literature research, we also found that silencing of SNHGs through small interfering RNAs or short hairpin RNAs is very effective in both in vitro and in vivo experiments by lowering the aggressiveness of solid cancers. The knockdown of SNHG as a new cancer therapeutic option should be investigated more in the future.
Collapse
Affiliation(s)
- Alina-Andreea Zimta
- Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Adrian Bogdan Tigu
- Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Cornelia Braicu
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Cristina Stefan
- African Organisation for Research and Training in Cancer, Cape Town, South Africa
| | - Calin Ionescu
- Surgical Department, Municipal Hospital, Cluj-Napoca, Romania
- Department of Surgery, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - Ioana Berindan-Neagoe
- Medfuture Research Center for Advanced Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
- Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
- Department of Functional Genomics and Experimental Pathology, The Oncology Institute “Prof. Dr. I. Chiricuta”, Cluj-Napoca, Romania
| |
Collapse
|
|
45
|
Wang Y, Huang Q, Li F. miR-140-5p targeted FGF9 and inhibited the cell growth of laryngeal squamous cell carcinoma. Biochem Cell Biol 2020; 98:83-89. [PMID: 31867983 DOI: 10.1139/bcb-2018-0351] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Increasing evidence has suggested that microRNAs (miRNAs) play critical roles in the initiation and development of cancers. Here, we found that miR-140-5p was significantly downregulated in both laryngeal squamous cell carcinoma (LSCC) tissues and cell lines. Decreased expression of miR-140-5p was significantly associated with the metastasis of LSCC. Overexpression of miR-140-5p inhibited proliferation and induced apoptosis of LSCC cells. Mechanistically, the fibroblast growth factor 9 (FGF9) was identified as the target of miR-140-5p. miR-140-5p bound the 3′-untranslated region (3′-UTR) of FGF9 and suppressed the expression of FGF9 in LSCC cells. Additionally, the level of FGF9 was upregulated in LSCC tissues and negatively correlated with the expression of miR-140-5p. Restoration of FGF9 attenuated the suppressive role of miR-140-5p in regulating the growth of LSCC cells. Collectively, these results indicated that the tumor suppressive function of miR-140-5p in LSCC was partially exercised by modulating the expression of FGF9.
Collapse
Affiliation(s)
- Ying Wang
- Department of Otolaryngology, Liaocheng People’s Hospital and EENT Hospital, Liaocheng Clinical School of Taishan Medical University, Liaocheng, 252000 Shandong, P.R. China
| | - Qingli Huang
- Department of Otolaryngology, Liaocheng People’s Hospital and EENT Hospital, Liaocheng Clinical School of Taishan Medical University, Liaocheng, 252000 Shandong, P.R. China
| | - Faping Li
- Department of Otolaryngology Head and Neck, Guangdong General Hospital and Guangdong Academy of Medical Sciences, Guangzhou, 510080 Guangdong, P.R. China
| |
Collapse
|
|
46
|
Talebi A, Masoodi M, Mirzaei A, Mehrad-Majd H, Azizpour M, Akbari A. Biological and clinical relevance of metastasis-associated long noncoding RNAs in esophageal squamous cell carcinoma: A systematic review. J Cell Physiol 2020; 235:848-868. [PMID: 31310341 DOI: 10.1002/jcp.29083] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2019] [Accepted: 06/21/2019] [Indexed: 12/12/2022]
Abstract
Esophageal squamous cell carcinoma (ESCC) is a foremost cancer-related death worldwide owing to rapid metastasis and poor prognosis. Metastasis, as the most important reason for death, is biologically a multifaceted process involving a range of cell signaling pathways. Long noncoding RNAs (lncRNAs), as transcriptional regulators, can regulate numerous genomic processes and cellular processes such as cell proliferation, migration, and invasion. LncRNAs have also been shown to involve in/regulate the cancer metastasis-related signaling pathways. Hence, they have increasingly been brought to international attention in molecular oncology research. A number of researchers have attempted to reveal the biological and clinical relevance of lncRNAs in ESCC tumourigenesis and metastasis. The aberrant expression of these molecules in ESCC has regularly been reported to involve in various cellular processes and clinical features, including diagnosis, prognosis, and therapeutic responses. Here, we especially consider the pathways in which lncRNAs act as metastasis-mediated effectors, mainly by interacting with epithelial-mesenchymal transition-associated factors. We review the biological roles of lncRNAs through involving in ESCC metastasis as well as the clinical significance of the metastasis-related lncRNAs in cancer diagnosis and prognosis.
Collapse
Affiliation(s)
- Atefeh Talebi
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Mohsen Masoodi
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Alireza Mirzaei
- Bone and Joint Reconstruction Research Center, Shafa Orthopedic Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Hassan Mehrad-Majd
- Cancer Molecular Pathology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mazaher Azizpour
- Department of Orthopedic Surgery, Aarhus University Hospital, Aarhus, Denmark
| | - Abolfazl Akbari
- Colorectal Research Center, Iran University of Medical Sciences, Tehran, Iran
| |
Collapse
|
|
47
|
Dai Y, Zhang X, Xing H, Zhang Y, Cao H, Sang J, Gao L, Wang L. Downregulated long non-coding RNA SNHG7 restricts proliferation and boosts apoptosis of nasopharyngeal carcinoma cells by elevating microRNA-140-5p to suppress GLI3 expression. Cell Cycle 2020; 19:448-463. [PMID: 31944163 PMCID: PMC7100885 DOI: 10.1080/15384101.2020.1712033] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Long non-coding RNAs (lncRNAs) have been proposed to correlate with various carcinomas, yet the role of lncRNA SNHG7 in nasopharyngeal carcinoma (NPC) is hardly studied. This study intends to examine the molecular mechanism of SNHG7 on NPC cells. The NPC tissues and nasopharyngeal tissues of mild inflammation of nasopharyngeal mucosa were obtained. SNHG7, miR-140-5p, and GLI3 mRNA and protein expression in tissues and in the CNE1, HONE1, C666-1, CNE2, and normal NP69 cell lines was detected. IC50 and the protein expression of related drug-resistant genes of CNE2 and CNE2/DDP cells were determined. Proliferative ability, cell colony formation rate, cell cycle, and apoptosis of CNE2 and CNE2/DDP cells were also detected. SNHG7, miR-140-5p, and GLI3 mRNA and protein expression in CNE2 and CNE2/DDP cells in each group was detected. SNHG7’s cell localization, the binding sites of SNHG7 and miR-140-5p along with miR-140-5p and GLI3 were detected. Overexpressed SNHG7 and GLI3, and underexpressed miR-140-5p were found in NPC tissues and cells. SNHG7 silencing and miR-140-5p elevation declined the drug resistance of drug-resistant NPC cells and their parent cells, restrained NPC cell colony formation ability and proliferation, and boosted cell apoptosis. SNHG7 specially bound to miR-140-5p, and SNHG7 silencing elevated miR-140-5p expression. GLI3 was a direct target gene of miR-140-5p and miR-140-5p elevation diminished GLI3 expression. MiR-140-5p inhibition reversed the impacts of SNHG7 silencing on NPC cells. In summary, our study reveals that downregulated SNHG7 restricts GLI3 expression by upregulating miR-140-5p, which further suppresses cell proliferation, and promotes apoptosis of NPC.
Collapse
Affiliation(s)
- Yaozhang Dai
- Department of Throat, Head and Neck Surgery, Affiliated Otolaryngological Hospital, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR.China
| | - Xin Zhang
- Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, PR.China
| | - Haijie Xing
- Department of Otolaryngology Head and Neck Surgery, University of Chinese Academy of Sciences, Shenzhen hospital, Shenzhen, Guangdong, PR.China
| | - Yamin Zhang
- Department of Throat, Head and Neck Surgery, Affiliated Otolaryngological Hospital, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR.China
| | - Hua Cao
- Department of Throat, Head and Neck Surgery, Affiliated Otolaryngological Hospital, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR.China
| | - Jianzhong Sang
- Department of Throat, Head and Neck Surgery, Affiliated Otolaryngological Hospital, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR.China
| | - Ling Gao
- Department of Throat, Head and Neck Surgery, Affiliated Otolaryngological Hospital, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR.China
| | - Liuzhong Wang
- Department of Throat, Head and Neck Surgery, Affiliated Otolaryngological Hospital, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, PR.China
| |
Collapse
|
|
48
|
Role of SNHG16 in human cancer. Clin Chim Acta 2019; 503:175-180. [PMID: 31901482 DOI: 10.1016/j.cca.2019.12.023] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2019] [Revised: 12/27/2019] [Accepted: 12/30/2019] [Indexed: 01/27/2023]
Abstract
A growing body of evidence suggests that long non-coding RNAs (lncRNAs), a novel class of non-coding endogenous single-stranded RNA, play a key role in multiple physiological and pathological processes through transcriptional interference, post-transcriptional regulation, and epigenetic modification. Furthermore, many studies have shown that lncRNAs-as oncogenes or tumour suppressors-play an important role in the occurrence and development of human cancers. Small nucleolar RNA host gene 16 (SNHG16) was initially identified as an oncogenic lncRNA in neuroblastoma, and has since been identified as a carcinogenic regulator of various malignant tumours. Overexpression of SNHG16 is associated with clinical and pathological characteristics of cancer patients, and regulates cell proliferation, apoptosis, invasion and metastasis through a variety of potential mechanisms. Therefore, SNHG16 may be a promising biomarker and therapeutic target for cancers. In this review, we summarize the biological function, related mechanisms and potential clinical significance of SNHG16 in multiple human cancers.
Collapse
|
|
49
|
Emerging Role of Non-Coding RNAs in Esophageal Squamous Cell Carcinoma. Int J Mol Sci 2019; 21:ijms21010258. [PMID: 31905958 PMCID: PMC6982002 DOI: 10.3390/ijms21010258] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Revised: 12/04/2019] [Accepted: 12/14/2019] [Indexed: 12/14/2022] Open
Abstract
Esophageal squamous cell carcinoma (ESCC) is a highly prevalent tumor and is associated with ethnicity, genetics, and dietary intake. Non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), long ncRNAs (lncRNAs), and circular RNAs (circRNAs) have been reported as functional regulatory molecules involved in the development of many human cancers, including ESCC. Recently, several ncRNAs have been detected as oncogenes or tumor suppressors in ESCC progression. These ncRNAs influence the expression of specific genes or their associated signaling pathways. Moreover, interactions of ncRNAs are evident in ESCC, as miRNAs regulate the expression of lncRNAs, and further, lncRNAs and circRNAs function as miRNA sponges to compete with the endogenous RNAs. Here, we discuss and summarize the findings of recent investigations into the role of ncRNAs (miRNAs, lncRNAs, and circRNAs) in the development and progression of ESCC and how their interactions regulate ESCC development.
Collapse
|
|
50
|
Yang H, Jiang Z, Wang S, Zhao Y, Song X, Xiao Y, Yang S. Long non-coding small nucleolar RNA host genes in digestive cancers. Cancer Med 2019; 8:7693-7704. [PMID: 31691514 PMCID: PMC6912041 DOI: 10.1002/cam4.2622] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2019] [Revised: 08/21/2019] [Accepted: 09/26/2019] [Indexed: 12/22/2022] Open
Abstract
Although long noncoding RNAs (lncRNAs) do not have protein coding capacities, they are involved in the pathogenesis of many types of cancers, including hepatocellular carcinoma, cervical cancer, and gastric cancer. Notably, the roles of lncRNAs are vital in nearly every aspect of tumor biology. Long non-coding small nucleolar RNA host genes (lnc-SNHGs) are abnormally expressed in multiple cancers, including urologic neoplasms, respiratory tumors, and digestive cancers, and play vital roles in these cancers. These host genes could participate in tumorigenesis by regulating proliferation, migration, invasion and apoptosis of tumor cells. This review focuses on the overview of the roles that lnc-SNHGs play in the formation and progression of digestive cancers.
Collapse
Affiliation(s)
- Huan Yang
- Department of GastroenterologyXinqiao HospitalArmy Medical UniversityChongqingChina
| | - Zheng Jiang
- Department of GastroenterologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqingChina
| | - Shuang Wang
- Department of GastroenterologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqingChina
- Department of GastroenterologyPeople's Hospital of Changshou ChongqingChongqingChina
| | - Yongbing Zhao
- Department of GastroenterologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqingChina
- Department of GastroenterologyPeople's Hospital of Changshou ChongqingChongqingChina
| | - Xiaomei Song
- Department of GastroenterologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqingChina
- Department of GastroenterologyPeople's Hospital of Changshou ChongqingChongqingChina
| | - Yufeng Xiao
- Department of GastroenterologyXinqiao HospitalArmy Medical UniversityChongqingChina
| | - Shiming Yang
- Department of GastroenterologyXinqiao HospitalArmy Medical UniversityChongqingChina
| |
Collapse
|