Nuclear miR-150 enhances hepatic lipid accumulation by targeting RNA transcripts overlapping the PLIN2 promoter

Abstract

Alcohol-associated liver disease is a prevalent chronic liver disease caused by excessive ethanol consumption. This study aims to investigate the role of miR-150 in regulating hepatic lipid homeostasis in alcoholic fatty liver (AFL). miR-150 was mainly distributed in the nucleus of hepatocytes and correlated with the degree of liver injury. The decreased expression of miR-150 observed in AFL was a compensatory response to ethanol-induced hepatic steatosis. Overexpression of miR-150 facilitated hepatic lipid accumulation in cellulo and exacerbated ethanol-induced liver steatosis invivo. In silico analysis identified perilipin-2 (PLIN2) as a potential target gene of miR-150. miR-150 activated PLIN2 transcription by directly binding the RNA transcripts overlapping PLIN2 promoter and facilitating the recruitment of DNA helicase DHX9 and RNA polymeraseⅡ. Overall, our study provides fresh insights into the homeostasis regulation of hepatic steatosis induced by ethanol and identifies miR-150 as a pro-steatosis effector driving transcriptional PLIN2 gene activation.