LINC01018 attenuates hepatic lipid accumulation by inducing autophagy via DHX9 pathway in alcohol-associated liver...

Chronic excessive alcohol consumption leads to alcohol-associated liver disease(ALD), and its pathogenesis mechanism is related to abnormal autophagy caused by excess alcohol. However, the regulation mechanism in the progression of ALD is still not clear. LINC01018 is a liver-enriched lncRNA that plays pivotal roles in the pathogenesis of liver disease. Our study found that LINC01018 was significantly downregulated in the hepatic tissue of ALD patients. Further in vivo and in vitro studies indicated that overexpression of LINC01018 could inhibit ETOH-induced hepatic steatosis and lipid accumulation by promoting cell autophagy in ALD. RNA pull down and mass spectrometry analysis revealed that LINC01018 interacts with DHX9(DEAH-box helicase 9), which is an RNA helicase with RNA-binding activity that exerts pivotal influence on various aspects of RNA metabolism. Rescue experiments demonstrated that LINC01018 likely inhibited ETOH-induced hepatic steatosis through interaction with DHX9. Further investigation disclosed that DHX9 knockdown led to increased ATG12 and ATG5 levels, suggesting its potential role in modulating autophagy in ALD. Taken together, our findings revealed that LINC01018 attenuates hepatic lipid accumulation in ALD by inducing autophagy via DHX9, suggesting the potential of LINC01018 as a promising therapeutic target for the prevention and treatment of ALD.