Identify Functional lncRNAs in Nonalcoholic Fatty Liver Disease by Constructing a ceRNA Network

Aim: To identify functional long noncoding RNAs (lncRNAs) by constructing a NAFLD-related lncRNA–miRNA–mRNA network (NLMMN) based on the hypothesis that lncRNAs, as competitive endogenous RNAs (ceRNAs), are able to regulate mRNA functions by competitive binding to shared miRNAs. Methods: The “Limma R package” was used to identify differentially expressed lncRNAs and mRNAs (DElncRNAs and DEmRNAs). The “miRcode online tool” was used to predict the potential interactions between DElncRNAs or DEmRNAs using Perl, and “multiMiR R package” was used to predict the potential interactions between DElncRNAs and miRNAs. The NLMMN was viewed by Cytoscape. The DEmRNAs were further analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The real-time quantitative reverse transcription polymerase chain reaction (qRT–PCR) was used to identify functional lncRNAs in human liver tissue and FFAs-induced fat-overloading HepG2 cells. The role of functional lncRNA was explored in the HepG2 cell line. Results: A total of 336 DElncRNAs (154 upregulated and 182 downregulated, |log 2 (fold change) |>0.655 and P 0.608 and P Conclusion: LINC00240, RBMS3-AS3, and ALG9-IT1 might be novel functional lncRNAs that attenuate liver fibrosis in NAFLD by influencing the ECM through the ceRNA network. Among them, LINC00240 might have a key role.