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Sirtuin 2 (SIRT2) is a class III histone deacetylase that has been implicated to promote HCC development. However, the functional role of SIRT2 in HBV is still unclear. In this study, we found that HBV could upregulate SIRT2 expression. Additionally, HBx could activate SIRT2 promoter to upregulate the mRNA and protein level of SIRT2. Furthermore, we found that SIRT2 could facilitate HBV transcription and replication. Finally, we demonstrated that upregulation of SIRT2 by HBx promoted hepatocarcinogenesis. In summary, our findings revealed a novel function of SIRT2 in HBV and HBV-mediated HCC. First, SIRT2 could promote HBV replication. And then HBx-elevated SIRT2 could enhance the transformation of HBV-mediated HCC. Those findings highlight the potential role of SIRT2 in HBV and HBV-mediated HCC by interaction with HBx.

SIRT6 is a class III histone deacetylase that has been implicated in HCC development. We previously reported that SIRT6 potentiated apoptosis evasion in hepatocellular carcinoma by inhibiting both Bax expression and mitochondrial translocalization. However, the mechanism underlying SIRT6-mediated inhibition of Bax mitochondrial localization remains elusive. In this study, we found that although SIRT6 had no effect on the expression level of Ku70, SIRT6 could interact with Ku70 and deacetylate it. The increased acetylation of Ku70 in SIRT6-depleted cells disrupt its interaction with Bax, which finally resulted in Bax mitochondrial translocalization. Furthermore, lysine K542 on Ku70 was the target for deacetylation by SIRT6. Ku70K542Q mutation abolished suppression of association between Ku70 and Bax and caused redistribution of Bax to the cytosol in SIRT6-depleted cells. Finally, Ku70K542Q mutation could reversed the inhibition of growth and apoptosis promotion mediated by SIRT6 silencing. Together, our findings revealed SIRT6 could block the mitochondrial translocation of Bax and decrease the apoptotic ratio of HCC cells by deacetylation of Ku70. SIRT6 may serve as a promising target for developing targeted therapies for HCC in the future.