Comprehensive Bioinformatics Analysis of Critical Lncrnas, Mrnas and Mirnas in Non‑alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is the most common fatty liver disease in developed countries, in which fat accumulation in the liver is induced by non-alcoholic factors. The present study was conducted to identify NAFLD-associated long non-coding RNAs (lncRNAs), mRNAs and microRNAs (miRNAs). The microarray dataset GSE72756, which included 5 NAFLD liver tissues and 5 controls, was acquired from the Gene Expression Omnibus database. Differentially expressed lncRNAs (DE-lncRNAs) and mRNAs (DE-mRNAs) were detected using the pheatmap package. Using the clusterProfiler package and Cytoscape software, enrichment and protein-protein interaction (PPI) network analyses were conducted to evaluate the DE-mRNAs. Next, the miRNA-lncRNA-mRNA interaction network was visualized using Cytoscape software. Additionally, RP11-279F6.1 and AC004540.4 expression levels were analyzed by reverse transcription quantitative polymerase chain reaction. There were 318 DE-lncRNAs and 609 DE-mRNAs identified in the NAFLD tissues compared with the normal tissues. Jun proto-oncogene, AP-1 transcription factor subunit (JUN), which is regulated by AC004540.4 and RP11-279F6.1, exhibited higher degree compared with other nodes in the PPI network. Furthermore, miR-409-3p and miR-139 (targeting JUN) were predicted as PPI network nodes. In the miRNA-lncRNA-mRNA network, miR-20a and B-cell lymphoma 2-like 11 (BCL2L11) were among the top 10 nodes. Additionally, BCL2L11, AC004540.4 and RP11-279F6.1 were targeted by miR-20a, miR-409-3p and miR-139 in the miRNA-lncRNA-mRNA network, respectively. RP11-279F6.1 and AC004540.4 expression was markedly enhanced in NAFLD liver tissues. These key RNAs may be involved in the pathogenic mechanisms of NAFLD.