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

ABSTRACT

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 AC012668 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. AC012668 expression levels were significantly suppressed in NAFLD models, whereas AC012668 overexpression inhibited lipogenesis-related gene (SCD1, SREBP1, FAS) expression and TG/lipid accumulation in vitro. Subsequently, miR-380-5p was predicted and verified to target AC012668, and its expression was notably increased in the NAFLD cell model. Moreover, transfection of miR-380-5p antagonized the effects of AC012668 on lipid formation and accumulation. LRP2 was confirmed to be the target gene of miR-380-5p and was downregulated in the NAFLD cell model. Silencing LRP2 reversed the effects of the miR-380-5p inhibitor on lipid formation and accumulation. AC012668 inhibited NAFLD progression via the miR-380-5p/LRP2 axis. These findings may provide a novel strategy against NAFLD.

KEYWORDS:

• Nonalcoholic fatty liver disease
• long non-coding RNA
• miR-380-5p
• LRP2
• hepatic steatosis

Research highlights

1. miR-380-5p was verified to target AC012668

2. AC012668 expression was suppressed in NAFLD

3. LRP2 was confirmed to be the target gene of miR-380-5p

Disclosure statement

No potential conflict of interest was reported by the author(s).