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Ranjbar M, Heydarzadeh S, Shekari Khaniani M, Foruzandeh Z, Seif F, Pornour M, Rahmanpour D, Tarhriz V, Alivand M. Mutual interaction of lncRNAs and epigenetics: focusing on cancer. EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2023. [DOI: 10.1186/s43042-023-00404-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/08/2023] Open
Abstract
AbstractLong noncoding RNAs are characterized as noncoding transcripts longer than 200 nucleotides in response to a variety of functions within the cells. They are involved in almost all cellular mechanisms so as epigenetics. Given that epigenetics is an important phenomenon, which participates in the biology of complex diseases, many valuable studies have been performed to demonstrate the control status of lncRNAs and epigenetics. DNA methylation and histone modifications as epigenetic mechanisms can regulate the expression of lncRNAs by affecting their coding genes. Reciprocally, the three-dimensional structure of lncRNAs could mechanistically control the activity of epigenetic-related enzymes. Dysregulation in the mutual interaction between epigenetics and lncRNAs is one of the hallmarks of cancer. These mechanisms are either directly or indirectly involved in various cancer properties such as proliferation, apoptosis, invasion, and metastasis. For instance, lncRNA HOTAIR plays a role in regulating the expression of many genes by interacting with epigenetic factors such as DNA methyltransferases and EZH2, and thus plays a role in the initiation and progression of various cancers. Conversely, the expression of this lncRNA is also controlled by epigenetic factors. Therefore, focusing on this reciprocated interaction can apply to cancer management and the identification of prognostic, diagnostic, and druggable targets. In the current review, we discuss the reciprocal relationship between lncRNAs and epigenetic mechanisms to promote or prevent cancer progression and find new potent biomarkers and targets for cancer diagnosis and therapy.
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Taleb RSZ, Zeid AE, Nabil MA, Moez PE. Plasma Long Non-Coding RNA ZFAS1 as a Potential Diagnostic Biomarker for HCV-Related Hepatocellular Carcinoma. MOLECULAR GENETICS, MICROBIOLOGY AND VIROLOGY 2022. [DOI: 10.3103/s0891416822040061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/22/2023]
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Endothelial derived miRNA-9 mediated cardiac fibrosis in diabetes and its regulation by ZFAS1. PLoS One 2022; 17:e0276076. [PMID: 36240130 PMCID: PMC9565427 DOI: 10.1371/journal.pone.0276076] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 09/28/2022] [Indexed: 11/07/2022] Open
Abstract
Diabetic cardiomyopathy (DCM) is one of the most prevalent causes of morbidity and mortality in diabetic patients. Hyperglycemia induces increased expression/deposition of extracellular matrix (ECM) proteins including fibronectin (FN) and collagen (Col) and plays an important role in fibrosis in diabetic cardiomyopathy (DCM). The roles of RNAs including microRNA (miRNA) and long non-coding RNAs (lncRNA) have begun to be understood in many conditions. In this study, we investigated the role of a specific miRNA, miR-9, and its interactions with lncRNA ZFAS1 in mediating fibrosis in DCM. Treatment with 25 mM glucose (HG) decreased miR-9 expression and increased expressions of ZFAS1, ECM proteins and inflammatory markers, compared to 5 mM glucose (NG) in the HCMECs by using qRT-PCR. Glucose-induced upregulation of ECM proteins can be prevented by ZFAS1 siRNA or miR-9 mimic transfection. Luciferase assay was confirmed miR-9 binding to FN 3’-UTR. miR-9 expression can be regulated by ZFAS1 through polycomb repressive complex 2 (PRC2) components using RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays. In the in vivo experiment, hyperglycemia-induced the ECM production can be prevented by the miR-9 overexpression in the fibrosis in DCM. These studies showed a novel glucose-induced molecular mechanism in which ZFAS1 participates in the transcriptional regulation of ECM protein production in diabetes through miR-9.
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Shang H, Chen Y, Wang C, Zhang S, Wu B, Liang X, Liu Z, Wang Q, Cheng W. RNA-Seq Technology Reveals the Mechanism of SDT Combined With Novel Nanobubbles Against HCC. Front Mol Biosci 2022; 8:791331. [PMID: 35198599 PMCID: PMC8859324 DOI: 10.3389/fmolb.2021.791331] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2021] [Accepted: 12/27/2021] [Indexed: 01/05/2023] Open
Abstract
Sonodynamic therapy is widely used in the treatment and research of hepatocellular carcinoma. A novel targeted nanobubble complex mediated with Hematoporphyrin monomethyl ether and Lonidamine was structured as a sensitizer, characterized the properties, and studied the therapeutic effect on hepatocellular carcinoma. The complexes can promote the apoptosis of hepatocellular carcinoma cells and work better in combination with sonodynamic therapy. The differential expression of multiple types of RNA in hepatocellular carcinoma with sonodynamic therapy can be identified accurately with high-throughput RNA sequencing. The differential expressions of mRNA, lncRNA, and circRNA were analyzed by RNA-Seq. The enrichment analyses (Gene Ontology and KEGG) prompted the meaningful genes and pathways in the process of sonodynamic therapy in hepatocellular carcinoma cells. HMME-LND@C3F8-NBs conjugated with ultrasound is confirmed efficiently for inhibiting the development of hepatocellular carcinoma cells, and it is a combination of multiple genes and mechanisms.
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Affiliation(s)
- Haitao Shang
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yichi Chen
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China
| | - Chunyue Wang
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China
| | - Shentao Zhang
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China
| | - Bolin Wu
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China
- Department of Interventional Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China
| | - Xitian Liang
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China
| | - Zhao Liu
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China
| | - Qiucheng Wang
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China
| | - Wen Cheng
- Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China
- Department of Interventional Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China
- *Correspondence: Wen Cheng,
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DiStefano JK, Gerhard GS. Long Noncoding RNAs and Human Liver Disease. ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE 2021; 17:1-21. [PMID: 34416820 DOI: 10.1146/annurev-pathol-042320-115255] [Citation(s) in RCA: 39] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Abstract
Long noncoding RNAs (lncRNAs) are pervasively transcribed in the genome, exhibit a diverse range of biological functions, and exert effects through a variety of mechanisms. The sheer number of lncRNAs in the human genome has raised important questions about their potential biological significance and roles in human health and disease. Technological and computational advances have enabled functional annotation of a large number of lncRNAs. Though the number of publications related to lncRNAs has escalated in recent years, relatively few have focused on those involved in hepatic physiology and pathology. We provide an overview of evolving lncRNA classification systems and characteristics and highlight important advances in our understanding of the contribution of lncRNAs to liver disease, with a focus on nonalcoholic steatohepatitis, hepatocellular carcinoma, and cholestatic liver disease. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease, Volume 17 is January 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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Affiliation(s)
- Johanna K DiStefano
- Diabetes and Fibrotic Disease Research Unit, Translational Genomics Research Institute, Phoenix, Arizona 85004, USA;
| | - Glenn S Gerhard
- Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania 19140, USA;
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O'Brien SJ, Fiechter C, Burton J, Hallion J, Paas M, Patel A, Patel A, Rochet A, Scheurlen K, Gardner S, Eichenberger M, Sarojini H, Srivastava S, Rai S, Kalbfleisch T, Polk HC, Galandiuk S. Long non-coding RNA ZFAS1 is a major regulator of epithelial-mesenchymal transition through miR-200/ZEB1/E-cadherin, vimentin signaling in colon adenocarcinoma. Cell Death Discov 2021; 7:61. [PMID: 33771981 PMCID: PMC7998025 DOI: 10.1038/s41420-021-00427-x] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Revised: 12/12/2020] [Accepted: 02/03/2021] [Indexed: 12/13/2022] Open
Abstract
Colon adenocarcinoma is a common cause of cancer-related deaths worldwide. Epithelial-mesenchymal transition is a major regulator of cancer metastasis, and increased understanding of this process is essential to improve patient outcomes. Long non-coding RNA (lncRNA) are important regulators of carcinogenesis. To identify lncRNAs associated with colon carcinogenesis, we performed an exploratory differential gene expression analysis comparing paired colon adenocarcinoma and normal colon epithelium using an RNA-sequencing data set. This analysis identified lncRNA ZFAS1 as significantly increased in colon cancer compared to normal colon epithelium. This finding was validated in an institutional cohort using laser capture microdissection. ZFAS1 was also found to be principally located in the cellular cytoplasm. ZFAS1 knockdown was associated with decreased cellular proliferation, migration, and invasion in two colon cancer cell lines (HT29 and SW480). MicroRNA-200b and microRNA-200c (miR-200b and miR-200c) are experimentally validated targets of ZFAS1, and this interaction was confirmed using reciprocal gene knockdown. ZFAS1 knockdown regulated ZEB1 gene expression and downstream targets E-cadherin and vimentin. Knockdown of miR-200b or miR-200c reversed the effect of ZFAS1 knockdown in the ZEB1/E-cadherin, vimentin signaling cascade, and the effects of cellular migration and invasion, but not cellular proliferation. ZFAS1 knockdown was also associated with decreased tumor growth in an in vivo mouse model. These results demonstrate the critical importance of ZFAS1 as a regulator of the miR-200/ZEB1/E-cadherin, vimentin signaling cascade.
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Affiliation(s)
- Stephen J O'Brien
- Price Institute of Surgical Research, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40202, USA
| | - Casey Fiechter
- Price Institute of Surgical Research, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40202, USA
| | - James Burton
- Price Institute of Surgical Research, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40202, USA
| | - Jacob Hallion
- Price Institute of Surgical Research, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40202, USA
| | - Mason Paas
- Price Institute of Surgical Research, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40202, USA
| | - Ankur Patel
- Price Institute of Surgical Research, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40202, USA
| | - Ajay Patel
- Price Institute of Surgical Research, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40202, USA
| | - Andre Rochet
- Price Institute of Surgical Research, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40202, USA
| | - Katharina Scheurlen
- Price Institute of Surgical Research, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40202, USA
| | - Sarah Gardner
- Price Institute of Surgical Research, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40202, USA
| | - Maurice Eichenberger
- Price Institute of Surgical Research, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40202, USA
| | - Harshini Sarojini
- Price Institute of Surgical Research, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40202, USA
| | - Sudhir Srivastava
- Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY, USA
- Centre for Agricultural Bioinformatics, ICAR-Indian Agricultural Statistics Research Institute, New Delhi, India
| | - Shesh Rai
- Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY, USA
| | - Theodore Kalbfleisch
- Department of Veterinary Science, Gluck Equine Research Center, University of Kentucky, Lexington, KY, USA
| | - Hiram C Polk
- Price Institute of Surgical Research, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40202, USA
| | - Susan Galandiuk
- Price Institute of Surgical Research, Hiram C. Polk Jr. MD Department of Surgery, University of Louisville School of Medicine, Louisville, KY, 40202, USA.
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Yu Y, Lu W, Zhou X, Huang H, Shen S, Guo L. MicroRNA-132 suppresses migration and invasion of renal carcinoma cells. J Clin Lab Anal 2020; 34:e22969. [PMID: 31625200 PMCID: PMC6977305 DOI: 10.1002/jcla.22969] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Revised: 06/03/2019] [Accepted: 06/12/2019] [Indexed: 01/23/2023] Open
Abstract
BACKGROUND The aim of this study was to explain the effects of microRNA-132 in renal cell carcinoma by regulating FOXM1 expression. METHODS Thirty patients with renal cell carcinoma admitted to our hospital were enrolled, and their adjacent normal tissues and cancer tissues were taken. The expression of microRNA-132 was measured by in situ hybridization (ISH) and RT-PCR, and the expression of FOXM1 was evaluated by RT-PCR and immunohistochemistry (IHC), and the correlation between microRNA-132 and FOXM1 was analyzed. In the cell experiment, the KETR-3 cells were divided into three groups: Negative control (NC) group were treated with nothing; blank (BL) group were transfected with empty vector; and microRNA-132 (miRNA) group were transfected with microRNA-132. The cell invasion and migration abilities among groups were assessed by transwell and wound healing assays. The expression levels of related proteins (FOXM1, MMP-2, MMP-9, VEGF-alpha, and uPAR) were determined by Western blot. RESULTS Depending on clinical data, we found that FOXM1 protein expression of renal cell carcinoma tissues was higher than that in adjacent normal tissues. MiRNA-132 was negative correlation with FOXM1. In vitro, the number of invasive cells and wound healing rate in the microRNA group were significantly suppressed than those in the NC group (P < 0.05, respectively). In the Western blot assay, the results showed that the protein expression levels of FOXM1, MMP-2, MMP-9, VEGF-α, and uPAR were significantly inhibited in the miRNA group compared with the NC group (P < 0.05, respectively). CONCLUSION miRNA-132 had anti-tumor effects in renal cell carcinoma by suppressing FOXM1 expression.
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Affiliation(s)
- Yi Yu
- Department of UrologyThe Second Affiliated Hospital of Nanchang UniversityNanchangJiangxi ProvinceChina
| | - Wenbao Lu
- Department of UrologyThe Affiliated Hospital of Jiujiang University Clinical Medical CollegeJiujiangJiangxi ProvinceChina
| | - Xinmin Zhou
- Department of UrologyDuchang County Hospital of Traditional Chinese MedicineDuchangJiangxi ProvinceChina
| | - Hua Huang
- Department of UrologyThe Second Affiliated Hospital of Nanchang UniversityNanchangJiangxi ProvinceChina
| | - Shaochen Shen
- Department of UrologyThe Second Affiliated Hospital of Nanchang UniversityNanchangJiangxi ProvinceChina
| | - Lian Guo
- Department of AnesthesiaThe Second Affiliated Hospital of Nanchang UniversityNanchangJiangxi ProvinceChina
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Lian S, Li L, Zhou Y, Liu Z, Wang L. The co-expression networks of differentially expressed RBPs with TFs and LncRNAs related to clinical TNM stages of cancers. PeerJ 2019; 7:e7696. [PMID: 31576243 PMCID: PMC6753928 DOI: 10.7717/peerj.7696] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Accepted: 08/19/2019] [Indexed: 12/17/2022] Open
Abstract
BACKGROUND RNA-binding proteins (RBPs) play important roles in cellular homeostasis by regulating the expression of thousands of transcripts, which have been reported to be involved in human tumorigenesis. Despite previous reports of the dysregulation of RBPs in cancers, the degree of dysregulation of RBPs in cancers and the intrinsic relevance between dysregulated RBPs and clinical TNM information remains unknown. Furthermore, the co-expressed networks of dysregulated RBPs with transcriptional factors and lncRNAs also require further investigation. RESULTS Here, we firstly analyzed the deviations of expression levels of 1,542 RBPs from 20 cancer types and found that (1) RBPs are dysregulated in almost all 20 cancer types, especially in BLCA, COAD, READ, STAD, LUAD, LUSC and GBM with proportion of deviation larger than 300% compared with non-RBPs in normal tissues. (2) Up- and down-regulated RBPs also show opposed patterns of differential expression in cancers and normal tissues. In addition, down-regulated RBPs show a greater degree of dysregulated expression than up-regulated RBPs do. Secondly, we analyzed the intrinsic relevance between dysregulated RBPs and clinical TNM information and found that (3) Clinical TNM information for two cancer types-CHOL and KICH-is shown to be closely related to patterns of differentially expressed RBPs (DE RBPs) by co-expression cluster analysis. Thirdly, we identified ten key RBPs (seven down-regulated and three up-regulated) in CHOL and seven key RBPs (five down-regulated and two up-regulated) in KICH by analyzing co-expression correlation networks. Fourthly, we constructed the co-expression networks of key RBPs between 1,570 TFs and 4,147 lncRNAs for CHOL and KICH, respectively. CONCLUSIONS These results may provide an insight into the understanding of the functions of RBPs in human carcinogenesis. Furthermore, key RBPs and the co-expressed networks offer useful information for potential prognostic biomarkers and therapeutic targets for patients with cancers at the N and M stages in two cancer types CHOL and KICH.
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Affiliation(s)
- Shuaibin Lian
- College of Physics and Electronic Engineering, XinYang Normal University, Xinyang, HeNan, China
| | - Liansheng Li
- College of Life Sciences, XinYang Normal University, Xinyang, HeNan, China
| | - Yongjie Zhou
- College of Physics and Electronic Engineering, XinYang Normal University, Xinyang, HeNan, China
| | - Zixiao Liu
- College of Physics and Electronic Engineering, XinYang Normal University, Xinyang, HeNan, China
| | - Lei Wang
- College of Life Sciences, XinYang Normal University, Xinyang, HeNan, China
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Hamada H, Yamamura M, Ohi H, Kobayashi Y, Niwa K, Oyama T, Mano Y, Asai M, Tanuma SI, Uchiumi F. Characterization of the human zinc finger nfx‑1‑type containing 1 encoding ZNFX1 gene and its response to 12‑O‑tetradecanoyl‑13‑acetate in HL‑60 cells. Int J Oncol 2019; 55:896-904. [PMID: 31432148 DOI: 10.3892/ijo.2019.4860] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2019] [Accepted: 07/19/2019] [Indexed: 11/06/2022] Open
Abstract
Human promyelocytic HL‑60 cells can be differentiated into macrophage‑like cells by treatment with 12‑O‑tetra decanoylphorbol‑13‑acetate (TPA). Certain 5' upstream regions of the zinc finger protein (ZNF)‑encoding genes contain duplicated GGAA motifs, which are frequently found in the TPA‑responding gene promoter regions. To examine transcriptional responses to TPA, 5'flanking regions of human zinc finger CCCH‑type containing, antiviral, ZNF252, ZNF343, ZNF555, ZNF782 and zinc finger nfx‑1‑type containing 1 (ZNFX1) genes were isolated by polymerase chain reaction (PCR) and ligated into a multiple‑cloning site of the pGL4.10[luc2] vector. Transient transfection and a luciferase assay revealed that the ZNFX1 promoter most prominently responded to the TPA treatment. Deletion and point mutation experiments indicated that the duplicated GGAA motif in the 100‑bp region positively responded to TPA. In addition, reverse transcription‑quantitative PCR and western blotting showed that the mRNA and protein of ZNFX1 accumulate during the differentiation of HL‑60 cells. These results indicated that expression of the TPA‑inducible ZNFX1 gene, which belongs to the group of interferon‑responsive genes, is regulated by the cis‑action of the duplicated GGAA motif.
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Affiliation(s)
- Hiroshi Hamada
- Department of Gene Regulation, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda‑shi, Chiba‑ken 278‑8510, Japan
| | - Mayu Yamamura
- Department of Gene Regulation, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda‑shi, Chiba‑ken 278‑8510, Japan
| | - Hiroto Ohi
- Department of Gene Regulation, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda‑shi, Chiba‑ken 278‑8510, Japan
| | - Yota Kobayashi
- Department of Gene Regulation, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda‑shi, Chiba‑ken 278‑8510, Japan
| | - Kuniyoshi Niwa
- Department of Gene Regulation, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda‑shi, Chiba‑ken 278‑8510, Japan
| | - Takahiro Oyama
- Department of Gene Regulation, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda‑shi, Chiba‑ken 278‑8510, Japan
| | - Yasunari Mano
- Department of Clinical Drug Informatics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda‑shi, Chiba‑ken 278‑8510, Japan
| | - Masashi Asai
- Department of Gene Regulation, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda‑shi, Chiba‑ken 278‑8510, Japan
| | - Sei-Ichi Tanuma
- Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda‑shi, Chiba‑ken 278‑8510, Japan
| | - Fumiaki Uchiumi
- Department of Gene Regulation, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda‑shi, Chiba‑ken 278‑8510, Japan
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Ma Y, Cao D, Li G, Hu J, Liu X, Liu J. Silence of lncRNA HEIH suppressed liver cancer cell growth and metastasis through miR-199a-3p/mTOR axis. J Cell Biochem 2019; 120:17757-17766. [PMID: 31144384 DOI: 10.1002/jcb.29041] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2018] [Revised: 05/05/2019] [Accepted: 05/07/2019] [Indexed: 12/15/2022]
Abstract
BACKGROUND/AIMS High expression in hepatocellular carcinoma (HEIH) is an long noncoding RNA (lncRNA) which is highly expressed in hepatocellular carcinoma (HCC). Aberrant expression of HEIH is implicated in regulating HCC cells growth and metastasis. This study attempted to illustrate the effects of HEIH on HCC cell lines. METHODS The expression changes of HEIH in HCC tumor tissues and the paracancerous tissues derived from 20 patients with HCC were tested. Effects of HEIH on Huh7 and Hep3B cells viability, apoptosis, migration, and invasion were assessed by silencing HEIH in vitro. Furthermore, downstream effector and signaling of HEIH were studied. RESULTS As compared with the paracancerous tissues, the HEIH expression was highly expressed in tumor tissues. Silence of HEIH significantly reduced Huh7 and Hep3B cells viability, migration, and invasion, but induced apoptosis. It was coupled with the downregulated CyclinD1, Bcl-2, MMP-2, MMP-8, Vimentin, the upregulated p53, Bax, as well as the cleaved caspase-3. MicroRNA (miR)-199a-3p was identified as a downstream effector of HEIH, as its expression was upregulated by HEIH silence, and the functional effects of HEIH on Huh7 and Hep3B cells were all attenuated when miR-199a-3p expression was suppressed. Furthermore, HEIH silence suppressed the activation of mTOR signaling via upregulating miR-199a-3p. CONCLUSION HEIH silence might be a promising target for suppressing HCC cells growth and metastasis. Silence of HEIH exerted its antitumor properties possibly through upregulating miR-199a-3p, and thereby blockage of mTOR signaling.
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Affiliation(s)
- Yongbiao Ma
- Department of Hepatobiliary Surgery, Weifang People's Hospital, Weifang, China
| | - De Cao
- Department of Anaesthesiology, Weifang People's Hospital, Weifang, China
| | - Gaoxue Li
- Department of Gastroenterology, Shouguang People's Hospital, Shouguang, China
| | - Jingxia Hu
- Department of General Surgery, Shouguang People's Hospital, Shouguang, China
| | - Xin Liu
- Department of Medical Oncology, Affiliated Hospital of Weifang Medical University, Weifang, China
| | - Jianling Liu
- Infection Management Office, Weifang People's Hospital, Weifang, China
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Kolenda T, Guglas K, Kopczyńska M, Teresiak A, Bliźniak R, Mackiewicz A, Lamperska K, Mackiewicz J. Oncogenic Role of ZFAS1 lncRNA in Head and Neck Squamous Cell Carcinomas. Cells 2019; 8:cells8040366. [PMID: 31010087 PMCID: PMC6523746 DOI: 10.3390/cells8040366] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2019] [Revised: 04/17/2019] [Accepted: 04/18/2019] [Indexed: 12/15/2022] Open
Abstract
Background: Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease with high mortality. The identification of specific HNSCC biomarkers will increase treatment efficacy and limit the toxicity of current therapeutic strategies. Long non-coding RNAs (lncRNAs) are promising biomarkers. Accordingly, here we investigate the biological role of ZFAS1 and its potential as a biomarker in HNSCC. Methods: The expression level of ZFAS1 in HNSCC cell lines was analyzed using qRT-PCR. Based on the HNSCC TCGA data, the ZFAS1 expression profile, clinicopathological features, and expression of correlated genes were analyzed in patient tissue samples. The selected genes were classified according to their biological function using the PANTHER tool. The interaction between lncRNA:miRNA and miRNA:mRNA was tested using available online tools. All statistical analyses were accomplished using GraphPad Prism 5. Results: The expression of ZFAS1 was up-regulated in the metastatic FaDu cell line relative to the less aggressive SCC-25 and SCC-040 and dysplastic DOK cell lines. The TCGA data indicated an up-regulation of ZFAS1 in HNSCCs compared to normal tissue samples. The ZFAS1 levels typically differed depending on the cancer stage and T-stage. Patients with a lower expression of ZFAS1 presented a slightly longer disease-free survival and overall survival. The analysis of genes associated with ZFAS1, as well its targets, indicate that they are linked with crucial cellular processes. In the group of patients with low expression of ZFAS1, we detected the up-regulation of suppressors and down-regulation of genes associated with epithelial-to-mesenchymal transition (EMT) process, metastases, and cancer-initiating cells. Moreover, the negative correlation between ZFAS1 and its host gene, ZNFX1, was observed. The analysis of interactions indicated that ZFAS1 has a binding sequence for miR-150-5p. The expression of ZFAS1 and miR-150-5p is negatively correlated in HNSCC patients. miR-150-5p can regulate the 3′UTR of EIF4E mRNA. In the group of patients with high expression of ZFAS1 and low expression of miR-150-5p, we detected an up-regulation of EIF4E. Conclusions: In HNSCC, ZFAS1 displays oncogenic properties, regulates important processes associated with EMT, cancer-initiating cells, and metastases, and might affect patients’ clinical outcomes. ZFAS1 likely regulates the cell phenotype through miR-150-5p and its downstream targets. Following further validation, ZFAS1 might prove a new and valuable biomarker.
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Affiliation(s)
- Tomasz Kolenda
- Department of Cancer Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, 8 Rokietnicka Street, 60-806 Poznan, Poland.
- Laboratory of Cancer Genetics, Greater Poland Cancer Centre, 15 Garbary Street, Room 5025, 61-866 Poznan, Poland.
| | - Kacper Guglas
- Laboratory of Cancer Genetics, Greater Poland Cancer Centre, 15 Garbary Street, Room 5025, 61-866 Poznan, Poland.
- Postgraduate School of Molecular Medicine, Medical University of Warsaw, 61 Zwirki i Wigury Street, 02-091 Warszawa, Poland.
| | - Magda Kopczyńska
- Department of Cancer Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, 8 Rokietnicka Street, 60-806 Poznan, Poland.
- Laboratory of Cancer Genetics, Greater Poland Cancer Centre, 15 Garbary Street, Room 5025, 61-866 Poznan, Poland.
| | - Anna Teresiak
- Laboratory of Cancer Genetics, Greater Poland Cancer Centre, 15 Garbary Street, Room 5025, 61-866 Poznan, Poland.
| | - Renata Bliźniak
- Laboratory of Cancer Genetics, Greater Poland Cancer Centre, 15 Garbary Street, Room 5025, 61-866 Poznan, Poland.
| | - Andrzej Mackiewicz
- Department of Cancer Immunology, Chair of Medical Biotechnology, Poznan University of Medical Sciences, 8 Rokietnicka Street, 60-806 Poznan, Poland.
- Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, 15 Garbary Street, 61-866 Poznan, Poland.
| | - Katarzyna Lamperska
- Laboratory of Cancer Genetics, Greater Poland Cancer Centre, 15 Garbary Street, Room 5025, 61-866 Poznan, Poland.
| | - Jacek Mackiewicz
- Department of Diagnostics and Cancer Immunology, Greater Poland Cancer Centre, 15 Garbary Street, 61-866 Poznan, Poland.
- Department of Medical and Experimental Oncology, Heliodor Swiecicki Clinical Hospital, Poznan University of Medical Sciences, 16/18 Grunwaldzka Street, 60-786 Poznan, Poland.
- Department of Biology and Environmental Sciences, Poznan University of Medical Sciences, 8 Rokietnicka Street, 60-806 Poznan, Poland.
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12
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Gugnoni M, Ciarrocchi A. Long Noncoding RNA and Epithelial Mesenchymal Transition in Cancer. Int J Mol Sci 2019; 20:ijms20081924. [PMID: 31003545 PMCID: PMC6515529 DOI: 10.3390/ijms20081924] [Citation(s) in RCA: 113] [Impact Index Per Article: 18.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Revised: 04/12/2019] [Accepted: 04/15/2019] [Indexed: 12/22/2022] Open
Abstract
Epithelial-mesenchymal transition (EMT) is a multistep process that allows epithelial cells to acquire mesenchymal properties. Fundamental in the early stages of embryonic development, this process is aberrantly activated in aggressive cancerous cells to gain motility and invasion capacity, thus promoting metastatic phenotypes. For this reason, EMT is a central topic in cancer research and its regulation by a plethora of mechanisms has been reported. Recently, genomic sequencing and functional genomic studies deepened our knowledge on the fundamental regulatory role of noncoding DNA. A large part of the genome is transcribed in an impressive number of noncoding RNAs. Among these, long noncoding RNAs (lncRNAs) have been reported to control several biological processes affecting gene expression at multiple levels from transcription to protein localization and stability. Up to now, more than 8000 lncRNAs were discovered as selectively expressed in cancer cells. Their elevated number and high expression specificity candidate these molecules as a valuable source of biomarkers and potential therapeutic targets. Rising evidence currently highlights a relevant function of lncRNAs on EMT regulation defining a new layer of involvement of these molecules in cancer biology. In this review we aim to summarize the findings on the role of lncRNAs on EMT regulation and to discuss their prospective potential value as biomarkers and therapeutic targets in cancer.
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Affiliation(s)
- Mila Gugnoni
- Laboratory of Translational Research, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy.
| | - Alessia Ciarrocchi
- Laboratory of Translational Research, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy.
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13
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Abstract
While only a small part of the human genome encodes for proteins, biological functions for the so-called junk genome are increasingly being recognized through high-throughput technologies and mechanistic experimental studies. Indeed, novel mechanisms of gene regulation are being discovered that require coordinated interaction between DNA, RNA, and proteins. Therefore, interdisciplinary efforts are still needed to decipher these complex transcriptional networks. In this review, we discuss how non-coding RNAs (ncRNAs) are epigenetically regulated in cancer and metastases and consequently how ncRNAs participate in the sculpting of the epigenetic profile of a cancer cell, thus modulating the expression of other RNA molecules. In the latter case, ncRNAs not only affect the DNA methylation status of certain genomic loci but also interact with histone-modifying complexes, changing the structure of the chromatin itself. We present several examples of epigenetic changes causing aberrant expression of ncRNAs in the context of tumor progression. Interestingly, there are also important epigenetic changes and transcriptional regulatory effects derived from their aberrant expression. As ncRNAs can also be used as biomarkers for diagnosis and prognosis or explored as potential targets, we present insights into the use of ncRNAs for targeted cancer therapy.
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Long non-coding RNA ZNFX1-AS1 promotes the tumor progression and metastasis of colorectal cancer by acting as a competing endogenous RNA of miR-144 to regulate EZH2 expression. Cell Death Dis 2019; 10:150. [PMID: 30770796 PMCID: PMC6377660 DOI: 10.1038/s41419-019-1332-8] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2018] [Revised: 12/05/2018] [Accepted: 01/02/2019] [Indexed: 02/07/2023]
Abstract
Mounting evidences indicated that long non-coding RNA is dysregulated and involved in the pathology of tumors. However, the role of lncRNAs in colorectal cancer (CRC) progression is not fully determined. Differentially expressed lncRNA profile in CRC was conducted by lncRNA microarray in 15 pairs of CRC tissues and adjacent normal tissues, and validated by real-time PCR analysis in another 106 pairs of tissues. The biological effect of lncRNA ZNFX1-AS1 was evaluated by in vitro and in vivo assays. The regulation between lncRNA ZNFX1-AS1 and miR-144 was evaluated by a series of experiments. We found that lncRNA ZNFX1-AS1 expression was significantly upregulated in CRC tissues and cell lines, and the expression of lncRNA ZNFX1-AS1 was associated with aggressive tumor phenotype and poor prognosis in CRC. Functionally, knockdown of lncRNA ZNFX1-AS1 inhibited cell proliferation, invasion, in vitro and tumorigenesis and metastasis in vivo. Further investigation demonstrated that lncRNA ZNFX1-AS1 functioned as a competing endogenous RNA (ceRNA) for miR-144, thereby leading to the depression of its endogenous target gene Polycomb group protein enhancer of zeste homolog 2 (EZH2). We found that lncRNA ZNFX1-AS1 is significantly upregulated in CRC, and the newly identified lncRNA ZNFX1-AS1-miR-144-EZH2 axis is involved in the regulation of CRC progression, which might be used as potential therapeutic targets for CRC patients.
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15
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Leng Y, Luo Q, Chen X, Chen F, Wang X, Pan Y. Clinicopathological and prognostic significance of zinc finger antisense 1 overexpression in cancers: A meta-analysis. Medicine (Baltimore) 2018; 97:e13378. [PMID: 30544408 PMCID: PMC6310591 DOI: 10.1097/md.0000000000013378] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
BACKGROUND An increasing number of studies have recently highlighted the role of zinc finger antisense 1(ZFAS1) as a prognostic marker in cancers. However, these results remain controversial. Hence, a meta-analysis was conducted to further investigate the effects of ZFAS1 expression on clinicopathological features and survival outcomes. METHOD All eligible studies were searched from PubMed, Embase, Web of Science, and the Cochrane Library. All included articles evaluated the relationship between the expression levels of ZFAS1 and survival, or the range of pathological features in cancer patients. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were computed to evaluate the effect of ZFAS1 expression on overall survival (OS), relapse-free survival (RFS), and disease-free survival (DFS). The relationship between ZFAS1 expression and clinicopathological features was determined through pooled odds ratios (ORs) and 95% CIs. RESULTS In total 8 studies, which comprised of 820 patients, were qualified for analysis. Results revealed that the overexpression of ZFAS1 was significantly associated with poor OS (HR = 1.97, 95% CI: 1.53-2.54), worse RFS (HR = 1.95, 95% CI: 1.24-3.04) and worse DFS (HR = 2.35, 95% CI: 1.43-3.88) in cancers. Further subgroup analysis revealed that ZFAS1 overexpression was significantly correlated with poor OS in different cancer types, HR obtain methods and sample sizes. In addition, this meta-analysis revealed that the upregulated expression of ZFAS1 was significantly associated with lymph node metastasis, Tumor Node Metastasis (TNM) stage, and tumor size. CONCLUSIONS This meta-analysis revealed that the expression of ZFAS1 was associated with tumor prognosis. ZFAS1 could be used as a predictor for tumor progression in various cancers.
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Affiliation(s)
- Yuanxiu Leng
- Department of Oncology Laboratory, Cancer Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, Zunyi
| | - Qing Luo
- Department of Oncology Laboratory, Cancer Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, Zunyi
| | - Xumei Chen
- Department of Oncology Laboratory, Cancer Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, Zunyi
| | - Fang Chen
- Department of Oncology Laboratory, Cancer Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, Zunyi
| | - Xue Wang
- Department of Oncology Laboratory, Cancer Hospital, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou Province, Zunyi
| | - Yana Pan
- Hematology and Oncology Department, The Fifth Affiliated Hospital of Zunyi Medical University, Zhuhai, Guangdong Province, Doumen District, Zhuhai,China
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16
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Abstract
Only a small fraction of the human genome corresponds to protein-coding genes. Historically, the vast majority of genomic sequence was dismissed as transcriptionally silent, but recent large-scale investigations have instead revealed a rich array of functionally significant elements, including non-protein-coding transcripts, within the noncoding regions of the human genome. Long noncoding RNAs (lncRNAs), a class of noncoding transcripts with lengths >200 nucleotides, are pervasively transcribed in the genome, and have been shown to bind DNA, RNA, and protein. LncRNAs exert effects through a variety of mechanisms that include guiding chromatin-modifying complexes to specific genomic loci, providing molecular scaffolds, modulating transcriptional programs, and regulating miRNA expression. An increasing number of experimental studies are providing evidence that lncRNAs mediate disease pathogenesis, thereby challenging the concept that protein-coding genes are the sole contributors to the development of human disease. This chapter highlights recent findings linking lncRNAs with human diseases of complex etiology, including hepatocellular carcinoma, Alzheimer's disease, and diabetes.
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17
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Dong D, Mu Z, Zhao C, Sun M. ZFAS1: a novel tumor-related long non-coding RNA. Cancer Cell Int 2018; 18:125. [PMID: 30186041 PMCID: PMC6122210 DOI: 10.1186/s12935-018-0623-y] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Accepted: 08/20/2018] [Indexed: 12/13/2022] Open
Abstract
Long non-coding RNAs (lncRNA) are classified as a kind of RNA, which are longer than 200 nucleotides in length and cannot be translated into proteins. Multiple studies have demonstrated that lncRNAs are involved in various cellular processes, including proliferation, differentiation, cell death, and metastasis. In addition, aberrant expression of lncRNAs has been discovered in human tumors, where they function as either oncogenes or tumor suppressor genes. Among numerous lncRNAs, we focus on ZNFX1 antisense RNA 1 (ZFAS1), a well-known lncRNA that is aberrant overexpression in various tumors, including melanoma, esophageal squamous cell carcinoma, non-small cell lung cancer, gastric cancer, colon cancer, and Hepatocellular carcinoma, in which it functions as oncogene. In contrast, ZFAS1 is downregulated in breast cancer, which may function as tumor suppressor gene. In this review, we provide an overview of current evidence concerning the role and potential clinical utilities of ZFAS1 in human cancers.
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Affiliation(s)
- Dan Dong
- 1Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, People's Republic of China
| | - Zhongyi Mu
- 3Department of Urology, Liaoning Cancer Hospital & Institute, Cancer Hospital of China Medical University, Shenyang, People's Republic of China
| | - Chenghai Zhao
- 1Department of Pathophysiology, College of Basic Medical Science, China Medical University, Shenyang, People's Republic of China
| | - Mingli Sun
- 2Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang, People's Republic of China
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18
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Hu X, Jiang J, Xu Q, Ni C, Yang L, Huang D. A Systematic Review of Long Noncoding RNAs in Hepatocellular Carcinoma: Molecular Mechanism and Clinical Implications. BIOMED RESEARCH INTERNATIONAL 2018; 2018:8126208. [PMID: 30105249 PMCID: PMC6076971 DOI: 10.1155/2018/8126208] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/22/2018] [Accepted: 04/10/2018] [Indexed: 02/07/2023]
Abstract
Hepatocellular carcinoma (HCC) has the second highest mortality rate worldwide among all cancers. Previous studies have revealed the significant involvement of long noncoding RNAs (lncRNAs) in numerous human cancers including HCC. Both oncogenic and tumor repressive lncRNAs have been identified and implicated in the complex process of hepatocarcinogenesis. They can be further explored as prospective diagnostic, prognostic, and therapeutic markers for HCC. An in-depth understanding of lncRNAs' mechanism in HCC is therefore required to fully explore their potential role. In the current review, we will concentrate on the underlying function, molecular mechanisms, and potential clinical implications of lncRNA in HCC.
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Affiliation(s)
- Xiaoge Hu
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
- Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
| | - Jiahong Jiang
- Department of Second Clinical Medical College, Zhejiang Chinese Medicine University, Hangzhou, Zhejiang 310053, China
| | - Qiuran Xu
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
- Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
| | - Chao Ni
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
- Department of General Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
| | - Liu Yang
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
- Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
| | - Dongsheng Huang
- Key Laboratory of Tumor Molecular Diagnosis and Individualized Medicine of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang 310014, China
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19
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Peng L, Yuan XQ, Zhang CY, Peng JY, Zhang YQ, Pan X, Li GC. The emergence of long non-coding RNAs in hepatocellular carcinoma: an update. J Cancer 2018; 9:2549-2558. [PMID: 30026854 PMCID: PMC6036883 DOI: 10.7150/jca.24560] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2017] [Accepted: 03/31/2018] [Indexed: 12/11/2022] Open
Abstract
Hepatocellular carcinoma (HCC) accounting for roughly 90% of all primary liver neoplasms is the sixth most frequent neoplasm and the second prominent reason of tumor fatality worldwide. As regulators of diverse biological processes, long non-coding RNAs (lncRNAs) are involved in onset and development of neoplasms. With the continuous booming of well-featured lncRNAs in HCC from 2016 to now, we reviewed the newly-presented comprehension about the relationship between lncRNAs and HCC in this study. To be specific, we summarized the overview function and study tools of lncRNAs, elaborated the roles of lncRNAs in HCC, and sketched the molecule mechanisms of lncRNAs in HCC. In addition, the application of lncRNAs serving as biomarkers in early diagnosis and outcome prediction of HCC patients was highlighted.
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Affiliation(s)
- Li Peng
- Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha 410078, P.R. China; Cancer Research Institute, Central South University, Changsha 410078, P.R. China
- Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P.R. China
| | - Xiao-Qing Yuan
- Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China
- Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong 510120, China
| | - Chao-Yang Zhang
- Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha 410078, P.R. China; Cancer Research Institute, Central South University, Changsha 410078, P.R. China
| | - Jiang-Yun Peng
- Guangdong Province Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Research Center of Medicine, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, P.R. China
| | - Ya-Qin Zhang
- Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha 410078, P.R. China; Cancer Research Institute, Central South University, Changsha 410078, P.R. China
| | - Xi Pan
- Department of Oncology, the third Xiangya Hospital, Central South University, Changsha 410013, P.R. China
| | - Guan-Cheng Li
- Key Laboratory of Carcinogenesis of the Chinese Ministry of Health and the Key Laboratory of Carcinogenesis and Cancer Invasion of Chinese Ministry of Education, Xiangya Hospital, Central South University, Changsha 410078, P.R. China; Cancer Research Institute, Central South University, Changsha 410078, P.R. China
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El Khodiry A, Afify M, El Tayebi HM. Behind the curtain of non-coding RNAs; long non-coding RNAs regulating hepatocarcinogenesis. World J Gastroenterol 2018; 24:549-572. [PMID: 29434445 PMCID: PMC5799857 DOI: 10.3748/wjg.v24.i5.549] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2017] [Revised: 01/17/2018] [Accepted: 01/23/2018] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the most common and aggressive cancers worldwide. HCC is the fifth common malignancy in the world and the second leading cause of cancer death in Asia. Long non-coding RNAs (lncRNAs) are RNAs with a length greater than 200 nucleotides that do not encode proteins. lncRNAs can regulate gene expression and protein synthesis in several ways by interacting with DNA, RNA and proteins in a sequence specific manner. They could regulate cellular and developmental processes through either gene inhibition or gene activation. Many studies have shown that dysregulation of lncRNAs is related to many human diseases such as cardiovascular diseases, genetic disorders, neurological diseases, immune mediated disorders and cancers. However, the study of lncRNAs is challenging as they are poorly conserved between species, their expression levels aren't as high as that of mRNAs and have great interpatient variations. The study of lncRNAs expression in cancers have been a breakthrough as it unveils potential biomarkers and drug targets for cancer therapy and helps understand the mechanism of pathogenesis. This review discusses many long non-coding RNAs and their contribution in HCC, their role in development, metastasis, and prognosis of HCC and how to regulate and target these lncRNAs as a therapeutic tool in HCC treatment in the future.
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Affiliation(s)
- Aya El Khodiry
- Genetic Pharmacology Research Group, Clinical Pharmacy Unit, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt
| | - Menna Afify
- Genetic Pharmacology Research Group, Clinical Pharmacy Unit, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt
| | - Hend M El Tayebi
- Genetic Pharmacology Research Group, Clinical Pharmacy Unit, Department of Pharmacology and Toxicology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo 11835, Egypt
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21
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Long noncoding RNAs in the initiation, progression, and metastasis of hepatocellular carcinoma. Noncoding RNA Res 2017; 2:129-136. [PMID: 30159431 PMCID: PMC6084840 DOI: 10.1016/j.ncrna.2017.11.001] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2017] [Revised: 11/27/2017] [Accepted: 11/27/2017] [Indexed: 12/19/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Despite awareness of risk factors for the development of HCC and advances in the diagnosis and clinical management of the disease, the molecular mechanisms underlying hepatocarcinogenesis remain poorly understood. Recent experimental studies provide strong evidence that long noncoding RNAs (lncRNAs), non-protein-coding transcripts with lengths >200 basepairs, contribute to the pathogenesis of numerous human diseases. Over the past decade, a role for lncRNAs in the initiation, progression, and metastasis of HCC has likewise emerged and developed into a highly active area of research. Although many lncRNAs appear to be dysregulated in HCC, extensive functional characterization has been performed on only a small proportion of these candidates to date. This review summarizes select lncRNAs that have been shown to wield functional relevance in the initiation, progression, or metastasis of HCC, focusing on the specific mechanisms by which lncRNA effects might be linked to clinical manifestations of the disease. In addition, an overview of circulating lncRNAs that have been identified as potential biomarkers for the diagnosis and prognosis of HCC is provided.
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