HCV core inhibits hepatocellular carcinoma cell replicative senescence through downregulating microRNA-138 expression

Hepatitis c virus (hcv) infection is a major cause of chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (hcc). hcv core protein is considered as a positive regulator of telomerase activity. in this study, we focused on the deregulated microrna-138 (mir-138) in hcv-associated hcc. differential expression of mir-138 was determined by taqman quantitative real-time pcr. the target gene of mir-138 was verified by luciferase reporter assay, quantitative real-time pcr, and western blotting. moreover, three assays based on telomerase activity, cell proliferation, and senescence-associated β-galactosidase activity were performed. the correlation analysis revealed a significantly negative correlation between mir-138 and telomerase reverse transcriptase (tert) mrna expression in hcc. further, we showed that mature hcv core protein of 173 amino acids, but not full-length form of 191 amino acids, suppressed mir-138 expression. tert was verified as a direct target of mir-138 in hcc cells. furthermore, tert-targeting mir-138 supplementation can prevent hcv core protein from repressing hcc cell replicative senescence. collectively, hcv core protein can enhance tert protein expression through downregulating tert-targeting mir-138 expression, which in turn inhibits hcc cell replicative senescence. this study further help our understanding on the pathogenic mechanisms of hcv core protein in hcv-associated hcc development.