MOF upregulates estrogen receptor α signaling pathway via its acetylase activity in hepatocellular carcinoma.

The histone acetyltransferase MOF (KAT8) is mainly involved in the acetylation of histone H4 at lysine 16 (H4K16) and some non-histone proteins. MOF expression level is significantly reduced in many cancers. However, the biological function of MOF and its underlying mechanism are yet elusive in hepatocellular carcinoma (HCC). Estrogen receptor α (ERα) has been considered as a tumor suppressor in HCC. Here, we have demonstrated that MOF expression is significantly reduced in HCC samples, and is positively correlated with that of ERα. MOF interacts with ERα, and participates in acetylation of ERα at K266, K268, K299, thereby inhibiting ERα ubiquitination to maintain the stability of ERα. Meanwhile, MOF participates in up-regulation of ERα-mediated transactivation. Depletion of MOF significantly promotes cell growth, migration and invasion in HCC cell lines. Taken together, our results provide the new insights to understand the mechanism underlying the modulation function of MOF on ERα action in HCC, suggesting that MOF might be a potential therapeutic target for HCC.