title: Coding and non-coding gene regulatory networks underlie the immune response in liver cirrhosis.
abstract: Liver cirrhosis is recognized as being the consequence of immune-mediated hepatocyte damage and repair processes. However, the regulation of these immune responses underlying liver cirrhosis has not been elucidated. In this study, we used GEO datasets and bioinformatics methods to established coding and non-coding gene regulatory networks including transcription factor-/lncRNA-microRNA-mRNA, and competing endogenous RNA interaction networks. Our results identified 2224 mRNAs, 70 lncRNAs and 46 microRNAs were differentially expressed in liver cirrhosis. The transcription factor -/lncRNA- microRNA-mRNA network we uncovered that results in immune-mediated liver cirrhosis is comprised of 5 core microRNAs (e.g., miR-203; miR-219-5p), 3 transcription factors (i.e., FOXP3, ETS1 and FOS) and 7 lncRNAs (e.g., ENTS00000671336, ENST00000575137). The competing endogenous RNA interaction network we identified includes a complex immune response regulatory subnetwork that controls the entire liver cirrhosis network. Additionally, we found 10 overlapping GO terms shared by both liver cirrhosis and hepatocellular carcinoma including "immune response" as well. Interestingly, the overlapping differentially expressed genes in liver cirrhosis and hepatocellular carcinoma were enriched in immune response-related functional terms. In summary, a complex gene regulatory network underlying immune response processes may play an important role in the development and progression of liver cirrhosis, and its development into hepatocellular carcinoma.
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.|Department of Pathology, The Research Institute of McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Bo
authors.identifier: http://orcid.org/0000-0003-3461-0096
authors.initials: B
authors.lastname: Gao
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Xueming
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Yongming
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Zhengpeng
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Traditional and Western Medical Hepatology, The Third Hospital of Hebei Medical University, Shijiazhuang, China.
authors.forename: Yuguo
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Weihui
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Pathology, The Research Institute of McGill University Health Centre, Montreal, Quebec, Canada.
authors.forename: Zu-Hua
authors.initials: ZH
authors.lastname: Gao
authors.affiliation: Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Dongbo
authors.initials: D
authors.lastname: Xue
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D019295:Computational Biology; D030541:Databases, Genetic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D053263:Gene Regulatory Networks / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000276:immunology; D062085:RNA, Long Noncoding / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics* / Q000276:immunology
chemical_list: D035683:MicroRNAs; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D014157:Transcription Factors