MicroRNA-572/hMOF/Sirt6 regulates the progression of ovarian cancer

Human males absent on the first (hMOF) is a histone acetyltransferase (HAT) and is involved in the pathogenesis of various cancers. This article aimed to reveal the potential mechanism of the miR-572/hMOF/Sirt6 axis in ovarian cancer (OC). In this study, we found that the mRNA and protein levels of hMOF and Sirt6 were abnormally down-regulated in OC tissues and cells. Further study indicated that the overexpression of hMOF increased the level of H4 histone acetylation in the Sirt6 promoter region and enhanced the ability of hMOF to bind to the Sirt6 promoter in OC cells, and repressed the proliferation of SKOV3 cells and promoted the apoptosis of SKOV3 cells via up-regulating Sirt6. Moreover, it was found that miR-572 negatively regulated hMOF luciferase activity. After the transfection of miR-572 inhibitor into SKOV3 cells, the cell proliferation was significantly repressed, while this repression was reversed after the transfection of shRNA-hMOF. Besides, the overexpression of hMOF could significantly inhibit the growth of tumors. Overall, our findings uncovered a novel regulatory pattern of hMOF in OC progression and provided new insights for relieving OC.

人类雄性缺失1蛋白（Human males absent on the first，hMOF）是一种组蛋白乙酰转移酶（histone acetyltransferase，HAT），参与多种癌症的发病进程。本研究旨在揭示微小RNA-572（miR-572）/hMOF/Sirt6轴在卵巢癌（ovarian cancer，OC）中的潜在作用机制。
本次研究发现，hMOF与Sirt6的mRNA及蛋白水平在卵巢癌组织与细胞中均存在异常下调。进一步机制探究显示，在卵巢癌细胞中，过表达hMOF可提升Sirt6启动子区域的H4组蛋白乙酰化水平，并增强hMOF与Sirt6启动子的结合能力；同时可通过上调Sirt6的表达，抑制SKOV3细胞的增殖并促进其凋亡。
此外，研究证实miR-572对hMOF的荧光素酶活性具有负向调控作用。将miR-572抑制剂转染至SKOV3细胞后，细胞增殖受到显著抑制，而这一抑制效应可通过转染靶向hMOF的短发夹RNA（shRNA-hMOF）得以逆转。
除此之外，过表达hMOF可显著抑制肿瘤生长。综上，本研究揭示了hMOF在卵巢癌进展中的全新调控模式，为卵巢癌的临床治疗提供了新的思路。