%0 Journal Article %A Jung, Jin Kyu %A Park, Sun-Hye %A Jang, Kyung Lib %T Hepatitis B virus X protein overcomes the growth-inhibitory potential of retinoic acid by downregulating retinoic acid receptor-β2 expression via DNA methylation %D 2010 %J Journal of General Virology, %V 91 %N 2 %P 493-500 %@ 1465-2099 %R https://doi.org/10.1099/vir.0.015149-0 %I Microbiology Society, %X Aberrant promoter methylation of retinoic acid receptor-β 2 (RAR-β 2) is frequently detected in hepatitis B virus (HBV)-positive hepatocellular carcinoma (HCC); however, the mechanism of methylation and its biological significance are unknown. This study showed that HBx, the principal oncogene product of HBV, induced promoter hypermethylation of RAR-β 2 via upregulation of DNA methyltransferases 1 and 3a, resulting in downregulation of its expression in human HCC cells. In addition, HBx abolished the potential of retinoic acid (RA) to downregulate levels of G1-checkpoint regulators including p16, p21 and p27, resulting in activation of E2F1 in the presence of RA. As a consequence, HBx-expressing cells were less susceptible to RA-induced cell growth inhibition compared with control cells. These effects almost completely disappeared when levels of RAR-β 2 in HBx-expressing cells were restored by treatment with a universal DNA methylation inhibitor, 5-aza-2′-deoxycytidine. As RAR-β 2 is a major executor of the anti-tumour potential of RA, its epigenetic downregulation by HBx is likely to be an important step during HBV-mediated tumorigenesis. %U https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.015149-0