Shao Genbao, Wan Xiaolei, Lai Wensheng, Wu Chaoyang, Jin Jie, Liu Xiuwen, Wei Ye, Lin Qiong, Zhang Liuping, Shao Qixiang
Department of Basic Medicine, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China.
Department of Oncology, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu 212002, P.R. China.
Oncol Lett. 2018 Jun;15(6):9025-9032. doi: 10.3892/ol.2018.8511. Epub 2018 Apr 17.
Lysine-specific demethylase 1 (LSD1) functions as a transcriptional coregulator by modulating histone methylation and has been associated with numerous high-risk cancers. Previously, our group and others identified LSD1 as an upregulated gene in ovarian cancer, and reported that the upregulation of LSD1 was associated with poor prognosis of patients with ovarian cancer. However, the role of LSD1 in ovarian cancer requires further investigation. The present study revealed that the overexpression of LSD1 significantly promoted the proliferation of SKOV3 ovarian cancer cells, while knockdown of LSD1 markedly inhibited cell proliferation and potentiated cisplatin-induced cell apoptosis, supporting LSD1 as an oncogenic protein in ovarian cancer. Mechanistic studies have indicated that LSD1 modulates the expression of cyclin dependent kinase inhibitor 1, Survivin, B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X genes, which are known regulators of cell proliferation. Furthermore, LSD1 knockdown plus cisplatin synergistically impaired cell migration via the induction of the epithelial marker E-cadherin and inhibition of the mesenchymal markers, snail family transcriptional repressor 1 and Vimentin. These data of the present study indicated LSD1 as a potential regulator of ovarian cancer cell progression and suggested an unfavorable role of LSD1 in cisplatin-based regimens.
赖氨酸特异性去甲基化酶1（LSD1）通过调节组蛋白甲基化发挥转录共调节因子的作用，并与多种高危癌症相关。此前，我们团队及其他研究团队将LSD1鉴定为卵巢癌中的一个上调基因，并报道LSD1的上调与卵巢癌患者的不良预后相关。然而，LSD1在卵巢癌中的作用仍需进一步研究。本研究表明，LSD1的过表达显著促进了SKOV3卵巢癌细胞的增殖，而敲低LSD1则明显抑制细胞增殖并增强顺铂诱导的细胞凋亡，这支持LSD1作为卵巢癌中的一种致癌蛋白。机制研究表明，LSD1调节细胞周期蛋白依赖性激酶抑制剂1、生存素、B细胞淋巴瘤-2（Bcl-2）和Bcl-2相关X基因的表达，这些基因是已知的细胞增殖调节因子。此外，敲低LSD1加顺铂通过诱导上皮标志物E-钙黏蛋白和抑制间充质标志物蜗牛家族转录抑制因子1和波形蛋白，协同损害细胞迁移。本研究的这些数据表明LSD1是卵巢癌细胞进展的潜在调节因子，并提示LSD1在基于顺铂的治疗方案中起不利作用。
