title: Transcriptional networks implicated in human nonalcoholic fatty liver disease.
abstract: The transcriptome of nonalcoholic fatty liver disease (NAFLD) was investigated in several studies. However, the implications of transcriptional networks in progressive NAFLD are not clear and mechanisms inducing transition from nonalcoholic simple fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) are still elusive. The aims of this study were to (1) construct networks for progressive NAFLD, (2) identify hub genes and functional modules in these networks and (3) infer potential linkages among hub genes, transcription factors and microRNAs (miRNA) for NAFLD progression. A systems biology approach by combining differential expression analysis and weighted gene co-expression network analysis (WGCNA) was utilized to dissect transcriptional profiles in 19 normal, 10 NAFL and 16 NASH patients. Based on this framework, 3 modules related to chromosome organization, proteasomal ubiquitin-dependent protein degradation and immune response were identified in NASH network. Furthermore, 9 modules of co-expressed genes associated with NAFL/NASH transition were found. Further characterization of these modules defined 13 highly connected hub genes in NAFLD progression network. Interestingly, 11 significantly changed miRNAs were predicted to target 10 of the 13 hub genes. Characterization of modules and hub genes that may be regulated by miRNAs could facilitate the identification of candidate genes and pathways responsible for NAFL/NASH transition and lead to a better understanding of NAFLD pathogenesis. The identified modules and hub genes may point to potential targets for therapeutic interventions.
authors: Department of Gastroenterology, Ningbo Medical Treatment Center Lihuili Hospital, Ningbo, 315040, China.
authors: Hua
authors: H
authors: Ye
authors: School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, China. antibodyliu@gmail.com.|Department of Pathology, Human Centrifuge Medical Training Center, Institute of Aviation Medicine of Chinese PLA Air Force, Beijing, 100089, China. antibodyliu@gmail.com.
authors: Wei
authors: W
authors: Liu
mesh_terms: D053263:Gene Regulatory Networks; D006801:Humans; D035683:MicroRNAs / Q000235:genetics; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D035683:MicroRNAs
keywords: Gene co-expression network; Hub gene; Nonalcoholic fatty liver disease; Transcriptome; microRNA