The regulation of miR-122 which is involved in Hepatitis C virus replication and interferon treatment response

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Mir-122 is a highly abundant and liver-specific miRNA, and reported to enhance Hepatitis C virus (HCV) replication and be associated with interferon treatment response and hepatocarcinogenesis. In this study, we investigated the regulation mechanism of miR-122. At first, we examined the correlation between the expression level of miR-122 and pri-miR-122 which was primary transcript of miR-122 in various hepatoma cell lines by realtime PCR. The result showed the positive correlation between miR-122 and pri-miR-122. Therefore, the expression level of pri-miR-122 was considered to be a major factor which determined that of miR-122. Next, we performed reporter gene assays integrated with truncation in the pri-miR-122 promoter, and determined the region which had high trans-activation effect. Next, we examined the DNA methylation status in the promoter region of pri-miR-122 by sodium bisulfite DNA sequencing, and found that the promoter region of pri-miR-122 was hyper-methylated in the hepatoma cell lines which have the low expression level of pri-miR-122. Moreover, with 5-aza-CdR treatment, the expression level of pri-miR-122 was increased in such cell lines. Therefore, the epigenetic regulation might play an important role in the expression of miR-122.