ATP Citrate Lyase and LncRNA NONMMUT010685 Play Crucial Role in Nonalcoholic Fatty Liver Disease Based on Analysis of Microarray Data

摘要

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease with unclear molecular mechanisms. Our study intended to identify potential long non-coding RNAs (lncRNAs) and genes, and to determine the potential molecular mechanisms of NAFLD pathogenesis. Methods: The microarrays of GSE24031 and GSE57425 were downloaded from the Gene Expression Omnibus database. GSE24031 included 4 control and 4 model mice and GSE57425 included 3 control and 3 model mice on the basis of GPL1261 platform. Differentially expressed lncRNAs and mRNAs between control and NAFLD liver tissue were calculated. Gene ontology (GO), pathway enrichment analyses, co-expression network and PPI were performed to analyze the biological roles and pathways for the differentially expressed lncRNAs and mRNAs. Non-alcoholic steatohepatitis (NASH) rats were further chosen to investigate the key protein identified based on co-expression network and protein-protein interaction (PPI) network data. Results: A total of 6 significantly up-regulated and 39 down-regulated lncRNAs, 340 up-regulated and 281 down-regulated mRNAs were identified. LncRNA-mRNA co-expression network were analyzed to show a total of 16 key lncRNAs (node degree > 10) in NAFLD samples compared to control tissues. Three key protein identified on co-expression network and protein-protein interaction (PPI) network data were verified in NASH in vivo. The protein level of ATP-citrate lyase (Acly) was significantly increased while lncNONMMUT010685 and NONMMUT050689 in NAFLD samples, whose regulator gene was x-box binding protein 1 (XBP1) and receptor-interacting protein 1 kinase (RIPK1) respectively, were gradually reduced in NASH. Conclusion: In summary, we found a set of lncRNAs and mRNAs differentially expressed in the development of NAFLD. LncRNA Ttc39aos1 and Acly, may be crucial biomarkers for NAFLD. LncRNA NONMMUT010685 and NONMMUT050689, the regulator of XBP1 gene and RIPK1 gene respectively, played important roles in the development of NAFLD.