MOF upregulates the estrogen receptor signaling pathway by its acetylase activity in hepatocellular carcinoma
CANCER SCIENCE(2021)
摘要
The histone acetyltransferase MOF (KAT8) is mainly involved in the acetylation of histone H4 at lysine 16 (H4K16) and some non-histone proteins. The MOF expression level is significantly reduced in many cancers, however the biological function of MOF and its underlying mechanism are still elusive in hepatocellular carcinoma (HCC). Estrogen receptor alpha (ER alpha) has been considered as a tumor suppressor in HCC. Here, we demonstrated that MOF expression is significantly reduced in HCC samples, and is positively correlated with that of ER alpha. MOF interacts with ER alpha, and participates in acetylation of ER alpha at K266, K268, K299, thereby inhibiting ER alpha ubiquitination to maintain the stability of ER alpha. In addition, MOF participates in the upregulation of ER alpha-mediated transactivation. Depletion of MOF significantly promotes cell growth, migration, and invasion in HCC cell lines. Taken together, our results provide new insights to understand the mechanism underlying the modulation function of MOF on ER alpha action in HCC, suggesting that MOF might be a potential therapeutic target for HCC.
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关键词
acetylation,estrogen receptor α,hepatocellular carcinoma,MOF,tumor suppression
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