MiR-625-5p regulates the development of non-alcoholic fatty liver disease by targeting CCND1

Abstract

Abstract Objectives Non-alcoholic fatty liver disease (NAFLD) exhibits a high prevalence globally. The pathogenesis of NAFLD is complex, and an increasing number of studies have indicated that dysregulation of miRNAs is implicated in this process. The aim of this study is to elucidate the function and regulatory mechanism of miR-625-5p in NAFLD. Methods The study included 112 patients with NAFLD and 106 control subjects. HepG2 cells and THLE-2 cells were induced to establish an NAFLD model by using a mixture of oleic acid (OA) and palmitic acid (PA). The expression levels of the target gene and inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α)] were detected using RT-qPCR. The receiver operating characteristic (ROC) curve and logistic regression analysis were utilized to evaluate the diagnostic value of miR-625-5p. The levels of triglyceride (TG), aspartate aminotransferase (AST)/alanine aminotransferase (ALT) enzyme activity, and apoptosis were measured. The target genes of miR-625-5p were predicted, and a Gene Ontology (GO) analysis was conducted. The binding reaction was assessed by a dual-luciferase reporter gene assay, and the correlation was analyzed through Spearman analysis. Results In NAFLD, the expression of miR-625-5p was significantly downregulated, which had potential diagnostic value for NAFLD. In the NAFLD cell model, the levels of TG, inflammatory factors, and liver injury all increased, yet they could be inhibited by the overexpressed miR-625-5p. MiR-625-5p bound to and negatively regulated CCND1. Upregulation of CCND1 could reverse the therapeutic effect of overexpressed miR-625-5p. Conclusions The downregulation of miR-625-5p may serve as a potential biomarker for the diagnosis of NAFLD. MiR-625-5p can impede lipid accumulation, inflammatory response, and liver damage in hepatocytes by negatively regulating CCND1.