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      Non-Coding RNAs and Hepatitis C Virus-Induced Hepatocellular Carcinoma

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          Abstract

          Hepatitis C virus (HCV) infection is a worldwide health problem and is one of the main causes of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Despite recent improvements, effective treatments for HCC are still missing and new tools for early detection are needed. Non-coding RNAs (ncRNAs) have emerged as important regulators of gene expression and key players in human carcinogenesis, including HCC. Aberrant expression of ncRNAs is associated with HCC metastasis, invasion, dissemination, and recurrence. This review will focus on the recent advances in ncRNA expression profiles, their dysregulation in HCV-related HCC, and the clinical perspective of ncRNA signatures for the early detection of HCC.

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          Most cited references72

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          The transcriptional landscape of the mammalian genome.

          P Carninci, T Kasukawa, S. Katayama … (2005)
          This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5' and 3' boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
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            RNA maps reveal new RNA classes and a possible function for pervasive transcription.

            Philipp Kapranov, Jill Cheng, Sujit Dike … (2007)
            Significant fractions of eukaryotic genomes give rise to RNA, much of which is unannotated and has reduced protein-coding potential. The genomic origins and the associations of human nuclear and cytosolic polyadenylated RNAs longer than 200 nucleotides (nt) and whole-cell RNAs less than 200 nt were investigated in this genome-wide study. Subcellular addresses for nucleotides present in detected RNAs were assigned, and their potential processing into short RNAs was investigated. Taken together, these observations suggest a novel role for some unannotated RNAs as primary transcripts for the production of short RNAs. Three potentially functional classes of RNAs have been identified, two of which are syntenically conserved and correlate with the expression state of protein-coding genes. These data support a highly interleaved organization of the human transcriptome.
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              A coding-independent function of gene and pseudogene mRNAs regulates tumour biology

              Laura Poliseno, Leonardo Salmena, JiangWen Zhang … (2010)
              The canonical role of messenger RNA (mRNA) is to deliver protein-coding information to sites of protein synthesis. However, given that microRNAs bind to RNAs, we hypothesized that RNAs possess a biological role in cancer cells that relies upon their ability to compete for microRNA binding and is independent of their protein-coding function. As a paradigm for the protein-coding-independent role of RNAs, we describe the functional relationship between the mRNAs produced by the PTEN tumour suppressor gene and its pseudogene (PTENP1) and the critical consequences of this interaction. We find that PTENP1 is biologically active as determined by its ability to regulate cellular levels of PTEN, and that it can exert a growth-suppressive role. We also show that PTENP1 locus is selectively lost in human cancer. We extend our analysis to other cancer-related genes that possess pseudogenes, such as oncogenic KRAS. Further, we demonstrate that the transcripts of protein coding genes such as PTEN are also biologically active. Together, these findings attribute a novel biological role to expressed pseudogenes, as they can regulate coding gene expression, and reveal a non-coding function for mRNAs.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Viruses
                Journal ID (iso-abbrev): Viruses
                Journal ID (publisher-id): viruses
                Title: Viruses
                Publisher: MDPI
                ISSN (Electronic): 1999-4915
                Publication date (Electronic): 30 October 2018
                Publication date Collection: November 2018
                Volume: 10
                Issue: 11
                Electronic Location Identifier: 591
                Affiliations
                [1 ]Cancer Research Center of Lyon (CRCL), UMR Inserm 1052 CNRS 5286 Mixte CLB, Université de Lyon 1 (UCBL1), 69003 Lyon, France; marie-laure.plissonnier@ 123456inserm.fr (M.-L.P.); massimo.levrero@ 123456inserm.fr (M.L.)
                [2 ]Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques, 67000 Strasbourg, France; katharina.herzog@ 123456etu.unistra.fr
                [3 ]Université de Strasbourg, 67000 Strasbourg, France
                [4 ]Hospices Civils de Lyon, Service d’Hépato-Gastroentérologie, 69004 Lyon, France
                Author notes
                [* ]Correspondence: mirjam.zeisel@ 123456inserm.fr ; Tel.: +33472681970
                Article
                Publisher ID: viruses-10-00591
                DOI: 10.3390/v10110591
                PMC ID: 6265700
                PubMed ID: 30380697
                SO-VID: bb4990cf-37ba-406a-8313-a7f5daa88f90
                Copyright © © 2018 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 16 October 2018
                Date accepted : 29 October 2018
                Categories
                Subject: Review

                ScienceOpen disciplines: Microbiology & Virology
                Keywords: hepatocellular carcinoma,hepatitis c virus,microrna,long non-coding rna
                Data availability:
                ScienceOpen disciplines: Microbiology & Virology
                Keywords: hepatocellular carcinoma, hepatitis c virus, microrna, long non-coding rna

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