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Journal of General Virology header logo Journal of General Virology

Volume 91, Issue 2

Hepatitis B virus X protein overcomes the growth-inhibitory potential of retinoic acid by downregulating retinoic acid receptor- expression via DNA methylation No Access

Abstract

Aberrant promoter methylation of retinoic acid receptor- (RAR- ) 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- 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 G-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- in HBx-expressing cells were restored by treatment with a universal DNA methylation inhibitor, 5-aza-2′-deoxycytidine. As RAR- 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.

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/content/journal/jgv/10.1099/vir.0.015149-0
2010-02-01
2026-01-17

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Hepatitis B virus X protein overcomes the growth-inhibitory potential of retinoic acid by downregulating retinoic acid receptor-β2 expression via DNA methylation
J. Gen. Virol. 91, 493 (2010); https://doi.org/10.1099/vir.0.015149-0
/content/journal/jgv/10.1099/vir.0.015149-0
/content/journal/jgv/10.1099/vir.0.015149-0
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