Long non-coding RNA AC012668 suppresses non-alcoholic fatty liver disease by competing for microRNA miR-380-5p with lipoprotein-related protein LRP2.

Nonalcoholic fatty liver disease (NAFLD) is characterized by high morbidity. Although long noncoding RNAs (lncRNAs) are known to have a role in NAFLD pathogenesis, the identified lncRNA types are limited. In this study, NAFLD models were established in vitro and in vivo using free fatty acid-treated LO2 cells and high-fat diet-fed mice, respectively. Microarray data were downloaded from the Gene Expression Omnibus database, and was selected for further analysis. Cell viability and apoptosis were measured using Cell Counting Kit 8 and flow cytometry assays. RNA expression was detected using reverse transcription-quantitative polymerase chain reaction. Triglyceride (TG) content and lipid deposition were detected using enzyme-linked immunosorbent assay and Oil-Red O staining. Western blotting was used to visualize protein expression. Starbase and TargetScan were used to predict the target miRNA and gene, and the predictions were verified through RNA pull-down and luciferase reporter assays. expression levels were significantly suppressed in NAFLD models, whereas overexpression inhibited lipogenesis-related gene () expression and TG/lipid accumulation in vitro. Subsequently, was predicted and verified to target , and its expression was notably increased in the NAFLD cell model. Moreover, transfection of antagonized the effects of on lipid formation and accumulation. was confirmed to be the target gene of and was downregulated in the NAFLD cell model. Silencing reversed the effects of the inhibitor on lipid formation and accumulation. inhibited NAFLD progression via the / axis. These findings may provide a novel strategy against NAFLD.