Long noncoding RNA CCAT1 inhibits miR-613 to promote nonalcoholic fatty liver disease via increasing LXRα transcription

Abstract

Nonalcoholic fatty liver disease (NAFLD) is regarded as a threat to public health; however, the pathologic mechanism of NAFLD is not fully understood. We attempted to identify abnormally expressed long noncoding RNA (lncRNAs) and messenger RNA that may affect the occurrence and development of NAFLD in this study. The expression of differentially expressed lncRNAs in NAFLD was determined in oleic acid (OA)-treated L02 cells, and the functions of CCAT1 in lipid droplet formation were evaluated in vitro. Differentially expressed genes (DEGs) were analyzed by microarray analysis, and DEGs related to CCTA1 were selected and verified by weighted correlation network analysis. The dynamic effects of LXR alpha and CCTA1 on lipid droplet formation and predicted binding was examined. The binding between miR-631 and CCAT1 and LXR alpha was verified. The dynamic effects of miR-613 inhibition and CCTA1 silencing on lipid droplet formation were examined. The expression and correlations of miR-631, CCAT1, and LXR alpha were determined in tissue samples. As the results show, CCAT1 was induced by OA and upregulated in NAFLD clinical samples. CCAT1 silencing significantly suppressed lipid droplet accumulation in vitro. LXR alpha was positively correlated with CCAT1. By inhibiting miR-613, CCAT1 increased the transcription of LXR alpha and promoted LXR alpha expression. The expression of LXR alpha was significantly increased in NAFLD tissues and was positively correlated with CCAT1. In conclusion, CCAT1 increases LXR alpha transcription by serving as a competing endogenous RNA for miR-613 in an LXRE-dependent manner, thereby promoting lipid droplet formation and NAFLD. CCAT1 and LXR alpha might be potent targets for NAFLD treatment.