Wang Xinjing, Li Bilan
Department of Gynecology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.
Onco Targets Ther. 2017 Mar 29;10:1865-1873. doi: 10.2147/OTT.S130022. eCollection 2017.
Endometrial carcinoma (EC) is the most common gynecologic malignancy, but the molecular events involved in the development and progression of EC remain unclear. This study aimed to investigate the role of DNA methyltransferase 1 (DNMT1), a member of DNA methyltransferases, in EC. AN3CA cells were transfected with DNMT1 siRNA. The proliferation, cell cycle, and apoptosis of AN3CA cells were evaluated by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. The expression of related genes was detected by polymerase chain reaction and Western blot analysis. Knockdown of DNMT1 inhibited the proliferation, induced apoptosis, and G0/G1 phase arrest of AN3CA cells. Furthermore, knockdown of DNMT1 upregulated the expression of nuclear factor kappa-B-inhibitor alpha (NF-κBIA) and Bax and downregulated the expression of Bcl-2 and CCND1/2 in AN3CA cells. In conclusion, this study provides the first evidence that knockdown of DNMT1 affects the expression of cell cycle- and apoptosis-associated proteins in EC cells, suggesting the potential of DNMT1 in EC therapy.
子宫内膜癌(EC)是最常见的妇科恶性肿瘤,但EC发生和发展过程中涉及的分子事件仍不清楚。本研究旨在探讨DNA甲基转移酶成员之一的DNA甲基转移酶1(DNMT1)在EC中的作用。用DNMT1小干扰RNA(siRNA)转染AN3CA细胞。通过细胞计数试剂盒-8(CCK-8)检测法和流式细胞术评估AN3CA细胞的增殖、细胞周期和凋亡情况。通过聚合酶链反应和蛋白质免疫印迹分析检测相关基因的表达。敲低DNMT1可抑制AN3CA细胞的增殖、诱导细胞凋亡并使其停滞于G0/G1期。此外,敲低DNMT1可上调AN3CA细胞中核因子κB抑制因子α(NF-κBIA)和Bax的表达,并下调Bcl-2和细胞周期蛋白D1/2(CCND1/2)的表达。总之,本研究首次证明敲低DNMT1会影响EC细胞中细胞周期和凋亡相关蛋白的表达,提示DNMT1在EC治疗中的潜在作用。