Identifying Autophagy-Related lncRNAs and Potential ceRNA Networks in NAFLD

Nonalcoholic fatty liver disease (NAFLD) is a common chronic disease with complex pathogenesis, which brings economic burden to the society, and there is still no effective therapy. Impaired autophagy has been implicated in the development of NAFLD. Long noncoding RNAs (lncRNAs) are also reported to play a role in the pathogenesis of NAFLD. However, the role of autophagy-related lncRNAs in NAFLD disease has not been elucidated. Here, we mined GSE135251, GSE160016, GSE130970 and GSE185062 datasets from the Gene Expression Omnibus database (GEO) and obtained the human autophagy-related gene list from the Human Autophagy Database (HADb) for in-depth bioinformatic analysis. Following differential expression analysis and intersection of the datasets, Pearson correlation analysis was performed on DElncRNAs and autophagy-related DEmRNAs to obtain autophagy-related lncRNAs, and then Starbase3.0 and TargetScan7.2 were used to construct competing endogenous RNAs (ceRNA) regulatory networks. We constructed four lncRNA-dominated ceRNA regulatory networks (PSMG3-AS1, MIRLET7BHG, RP11-136K7.2, LINC00925), and visualized with Cytoscape. Then we performed co-expression analysis of the ceRNA networks and autophagy-related genes, and functionally annotated them with Metascape. Finally, we performed receiver operating characteristic curve (ROC) analysis on lncRNAs and mRNAs within the ceRNA networks. Conclusively, our project is the first to study autophagy-related lncRNAs in NAFLD and finally mined four autophagy-related lncRNAs (PSMG3-AS1, MIRLET7BHG, RP11-136K7.2, LINC00925). We suggested that the four autophagy-related lncRNAs may be closely associated with the occurrence and development of NAFLD through the corresponding ceRNA regulatory networks. This research brings new horizons to the study of NAFLD.