Abstract
Ethanol (EtOH)-induced hepatic injury, characterized by hepatic steatosis with apoptosis, causes heavy health burden personally and socially. Long non-coding RNAs (lncRNAs) have been implicated in liver diseases. However, the role of lncRNA maternally expressed gene 3 (MEG3) in EtOH-induced hepatic injury remains unknown. The aim of present study was to assess the function of MEG3 and its functional interaction with miR-let-7c-5p in EtOH-induced hepatic injury. Here, we observed that MEG3 and NLRC5 expression was increased and miR-let-7c-5p expression decreased in EtOH-fed mice and EtOH-induced AML-12 cells. Knockdown of MEG3 contributed to attenuation of EtOH-induced steatosis and apoptosis in AML-12 cells. Also, expression level of MEG3 negatively correlated with miR-let-7c-5p expression and positively correlated with NLRC5 expression. In contrary to MEG3, miR-let-7c-5p overexpression attenuated EtOH-induced steatosis and apoptosis, as well as suppressed EtOH-induced increase in NLRC5 expression. By luciferase reporter assay, we concluded that miR-let-7c-5p directly binds to NLRC5 3′-UTR, thereby negatively regulates NLRC5 expression. Our data suggested that lncRNA MEG3 functions as a competing endogenous RNA for miR-let-7c-5p to regulate NLRC5 expression in EtOH-induced hepatic injury.
Highlights
Alcoholic liver disease (ALD) is associated with too much alcohol consumption and often presents after 20–30 years chronic abuse alcohol which is one of the predominant causes of liver-related morbidity and mortality worldwide (Dubuquoy, 2016)
We found that Long non-coding RNAs (lncRNAs) maternally expressed gene 3 (MEG3) was increased in EtOH-fed mice and EtOH-induced AML-12 cells
We demonstrated that MEG3 could directly bind to miR-let-7c-5p and effectively act as a sponge for miR-let-7c-5p to modulate the suppression of NLRC5
Summary
Alcoholic liver disease (ALD) is associated with too much alcohol consumption and often presents after 20–30 years chronic abuse alcohol which is one of the predominant causes of liver-related morbidity and mortality worldwide (Dubuquoy, 2016) It includes a broad clinical-histological from alcoholic steatosis, alcoholic hepatitis, cirrhosis to hepatocellular carcinoma. The mechanism underlying the role of MEG3 in EtOH-induced hepatic steatosis and apoptosis is inadequate. Recent studies proposed a viewpoint that lncRNA can suppress messenger RNA (mRNA) translation by microRNA (miRNA), resulting in increased expression of corresponding protein (Cai et al, 2017; Wang et al, 2017; Zhao et al, 2017). Previous studies from our laboratory have proved that NLRC5 plays a negative role in ethanol-induced hepatic steatosis. The MEG3/miR-let-7c-5p/NLRC5 axis functions as an important player in EtOH-induced hepatic steatosis and apoptosis
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