ABSTRACT

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.

摘要

第一个缺失的人类男性 (hMOF) 是一种组蛋白乙酰转移酶 (HAT)，它参与各种癌症的发病机制。本文旨在揭示 miR-572/hMOF/Sirt6 轴在卵巢癌 (OC) 中的潜在作用机制。在本研究中，我们发现 OC 组织和细胞中 hMOF 和 Sirt6 的 mRNA 和蛋白水平异常下调。进一步研究表明，hMOF的过表达增加了OC细胞Sirt6启动子区域H4组蛋白乙酰化水平，增强了hMOF与Sirt6启动子结合的能力，抑制了SKOV3细胞的增殖，促进了SKOV3细胞的凋亡。通过上调 Sirt6。此外，发现 miR-572 负调控 hMOF 荧光素酶活性。将 miR-572 抑制剂转染到 SKOV3 细胞后，细胞增殖被显着抑制，而这种抑制在转染shRNA-hMOF后被逆转。此外，hMOF的过表达可以显着抑制肿瘤的生长。总体而言，我们的研究结果揭示了一种新的 hMOF 在 OC 进展中的调节模式，并为缓解 OC 提供了新的见解。