Abstract
Persistent infection with the hepatitis B virus leads to liver cirrhosis and hepatocellular carcinoma. MicroRNAs (miRNAs) play an important role in a variety of biological processes; however, the role of miRNAs in chronic hepatitis B (CHB)‐induced liver damage remains poorly understood. Here, we investigated the role of miRNAs in CHB‐related liver damage. Microarray analysis of the expression of miRNAs in 22 CHB patients and 33 healthy individuals identified miR‐194 as one of six differentially expressed miRNAs. miR‐194 was up‐regulated in correlation with increased liver damage in the plasma or liver tissues of CHB patients. In mice subjected to 2/3 partial hepatectomy, miR‐194 was up‐regulated in liver tissues in correlation with hepatocyte growth and in parallel with the down‐regulation of the activin receptor ACVR2B. Overexpression of miR‐194 in human liver HL7702 cells down‐regulated ACVR2B mRNA and protein expression, promoted cell proliferation, acceleratedG1 to S cell cycle transition, and inhibited apoptosis, whereas knockdown of miR‐194 had the opposite effects. Luciferase reporter assays confirmed that ACVR2B is a direct target of miR‐194, and overexpression of ACVR2B significantly repressed cell proliferation and G1 to S phase transition and induced cell apoptosis. ACVR2B overexpression abolished the effect of miR‐194, indicating that miR‐194 promotes hepatocyte proliferation and inhibits apoptosis by down‐regulating ACVR2B. Taken together, these results indicate that miR‐194 plays a crucial role in hepatocyte proliferation and liver regeneration by targeting ACVR2B and may represent a novel therapeutic target for the treatment of CHB‐related liver damage.
Highlights
ACVR2B is down-regulated in colorectal carcinoma and in poorly differentiated endometrial carcinoma, whereas it is up-regulated in ovarian cancer cells compared with normal ovarian epithelial cells and in nephroblastoma.[35,36,37,38]
We examined the role of miR-194 in liver regeneration mediated by the modulation of its target ACVR2B
Our results showed that miR-194 was up-regulated in response to partial hepatectomy (PH), and the up-regulation was correlated with hepatocyte growth
Summary
Xue Gao and Pan Zhao contributed to this work and should be considered co-first authors. Infection with the hepatitis B virus (HBV), which affects more than 300 million people worldwide, can lead to acute or chronic infection, liver cirrhosis and primary liver cancer.[1,2] the percentage of patients progressing to liver disease or liver cancer is low, the. We expanded this work by exploring the role and mechanisms of miR-194, one of six differentially expressed miRNAs in CHB, and its target ACVR2B in liver injury and regeneration associated with CHB
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