LncRNA HOTAIR regulates the lipid accumulation in non-alcoholic fatty liver disease via miR-130b-3p/ROCK1 axis.

Background: Excessive hepatic lipid accumulation can lead to the occurrence of non-alcoholic fatty liver disease. Previous study showed that upregulation of lncRNA HOTAIR significantly increased total cholesterol and triglyceride. However, the function of HOTAIR in lipid accumulation during the progression NAFLD remains unclear.

Methods: High fat diet was used to mimic NAFLD in vivo, and free fatty acid was used to establish in vitro model of NAFLD. Oil red O staining was applied to test the lipid accumulation. The pathological changes in mice were observed by H&E staining. Western blot and qRT-PCR were applied to assess protein and mRNA levels, respectively. RIP assay was used to explore the relationship among HOTAIR, miR-130b-3p and ROCK1.

Results: The level of HOTAIR was upregulated in NAFLD. Downregulation of HOTAIR reversed lipid accumulation in FFA-treated HepG2 cells and primary hepatocytes. Meanwhile, HOTAIR bound with miR-130b-3p, and ROCK1 was identified to be the direct target of miR-130b-3p. Moreover, miR-130b-3p mimics-caused lipid accumulation decrease was reversed by pcDNA3.1-ROCK1. Furthermore, the effect of miR-130b-3p mimics on p-AMPK2α and ROCK1 level was partially reversed by ROCK1 overexpression.

Conclusion: Knockdown of HOTAIR significantly inhibited the progression of NAFLD through mediation of miR-130b-3p/ROCK1 axis. Our study might shed new lights on exploring new methods against NAFLD.