title: Identification of novel long non-coding RNAs deregulated in hepatocellular carcinoma using RNA-sequencing.
abstract: Functional characterization of long non-coding RNAs (lncRNAs) and their pathological relevance is still a challenging task. Abnormal expression of a few long non-coding RNAs have been found associated with hepatocellular carcinoma, with potential implications to both improve our understanding of molecular mechanism of liver carcinogenesis and to discover biomarkers for early diagnosis or therapy. However, the understanding of the global role of lncRNAs during HCC development is still in its infancy. In this study, we produced RNA-Seq data from 23 liver tissues (controls, cirrhotic and HCCs) and applied statistical and gene network analysis approaches to identify and characterize expressed lncRNAs. We detected 5,525 lncRNAs across different tissue types and identified 57 differentially expressed lncRNAs in HCC compared with adjacent non-tumour tissues using stringent criteria (FDR<0.05, Fold Change>2). Using weighted gene co-expression network analysis (WGCNA), we found that differentially expressed lncRNAs are co-expressed with genes involved in cell cycle regulation, TGF-β signalling and liver metabolism. Furthermore, we found that more than 20% of differentially expressed lncRNAs are associated to actively transcribed enhancers and that the co-expression patterns with their closest genes change dramatically during HCC development. Our study provides the most comprehensive compendium of lncRNAs expressed in HCC, as well as in control or cirrhotic livers. Our results identified both known oncogenic lncRNAs (such as H19 and CRNDE) and novel lncRNAs involved in cell cycle deregulation and liver metabolism deficits occurring during HCC development.
authors.affiliation: Epigenetics Group, International Agency for Research on Cancer (IARC), Lyon, France.
authors.forename: Davide Degli
authors.initials: DD
authors.lastname: Esposti
authors.affiliation: Epigenetics Group, International Agency for Research on Cancer (IARC), Lyon, France.
authors.forename: Hector
authors.initials: H
authors.lastname: Hernandez-Vargas
authors.affiliation: Genetic Cancer Susceptibility Group, International Agency for Research on Cancer (IARC), Lyon, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Voegele
authors.affiliation: Epigenetics Group, International Agency for Research on Cancer (IARC), Lyon, France.
authors.forename: Nora
authors.initials: N
authors.lastname: Fernandez-Jimenez
authors.affiliation: Genetic Cancer Susceptibility Group, International Agency for Research on Cancer (IARC), Lyon, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Forey
authors.affiliation: Centre de Recherche en Cancérologie de Lyon, UMR INSERM 1052, CNRS 5286, Lyon Cedex, France.|Hospices Civils de Lyon, Service d'Anatomopathologie, Groupement Hospitalier Lyon Nord, Lyon, France.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bancel
authors.affiliation: Genetic Cancer Susceptibility Group, International Agency for Research on Cancer (IARC), Lyon, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Le Calvez-Kelm
authors.affiliation: Genetic Cancer Susceptibility Group, International Agency for Research on Cancer (IARC), Lyon, France.
authors.forename: James
authors.initials: J
authors.lastname: McKay
authors.affiliation: Centre de Recherche en Cancérologie de Lyon, UMR INSERM 1052, CNRS 5286, Lyon Cedex, France.|Hospices Civils de Lyon, Service d'Hépatologie et de Gastroentérologie, Groupement Hospitalier Lyon Nord, Lyon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Merle
authors.affiliation: Epigenetics Group, International Agency for Research on Cancer (IARC), Lyon, France.
authors.forename: Zdenko
authors.initials: Z
authors.lastname: Herceg
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics* / Q000378:metabolism; D017423:Sequence Analysis, RNA; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D062085:RNA, Long Noncoding; D012334:RNA, Neoplasm
keywords: RNA-sequencing; enhancer-associated RNAs; gene networks; hepatocellular carcinoma; long non-coding RNA