MOF forms a positive feedback regulation with ER to suppress endometrial cancer progression

MOF is a histone acetyltransferase specific for H4K16 acetylation. It has been demonstrated that MOF is lower expressed in series of human cancers. However, the molecular mechanism underlying the detailed biological function of MOF in endometrial carcinomas (ECa) has not been fully defined. The estrogen receptor (ER) action plays a crucial role in endometrial cancer tumorigenesis and progression. Here, our data have demonstrated that estrogen/ER induces MOF gene transcription, meanwhile MOF stabilizes ER via acetylating ER in ECa, indicating that MOF forms a positive feedback loop with ER. In the whole genome-wide level, RNA microarray analyses have shown that MOF modulates a subset of endogenous ER-regulated genes, such as apoptosis associated factor DRAM1 and oncogene FXYD3. Knockdown of MOF leads to a G2/M cell cycle arrest and promotes ECa cell growth and proliferation. MOF depletion promotes xenograft tumor growth in mice. In addition, our results have demonstrated that MOF expression is lower in ECa than that in benign endometrial tissues. Importantly, the expression of MOF is positively correlated with that of ER in clinical samples. Cumulatively, our results suggest a positive feedback regulation involving MOF and ER is essential for suppression of endometrial cancer.

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