a Department of Pathology , Xiangya Hospital, School of Basic Medical Sciences, Central South University , Changsha , Hunan Province , China.
b School of Basic Medical Sciences , Central South University , Changsha , Hunan Province , China.
Cell Cycle. 2019 Jul;18(14):1601-1618. doi: 10.1080/15384101.2019.1624112. Epub 2019 Jun 9.
Ovarian cancer is one type of gynecological malignancies with extremely high lethal rate. Abnormal proliferation and metastasis are regarded to play important roles in patients' death, whereas we know little about the underlying molecular mechanisms. Under this circumstance, our current study aims to investigate the role of hub genes in ovarian cancer. Bioinformatics analysis of the data from GEO and analyses of ovarian cancer samples were performed. Then, the results showed that KIF23, a hub gene, was mainly related to cell cycle and positively associated with poor prognosis. Meanwhile, both miR-424-5p and miR-503-5p directly targeted to 3'UTR of KIF23 to suppress the expression of KIF23 and inhibit ovarian cancer cell proliferation and migration. Furthermore, we discovered that miR-424/503 was epigenetically repressed by hypermethylation in the promoter regions, which directly modulated the expression of KIF23 to improve the oncogenic performance of cancer cells in vitro. Together, our research certifies that miR-424/503 cluster is silenced by DNA hypermethylation, which promotes the expression of KIF23, thereby regulating the proliferation and migration of ovarian cancer cells. Interposing this process might be a novel approach in cancer therapy.
卵巢癌是一种具有极高致死率的妇科恶性肿瘤。异常增殖和转移被认为在患者死亡中起着重要作用，而我们对其潜在的分子机制知之甚少。在这种情况下，我们目前的研究旨在探讨卵巢癌中枢纽基因的作用。对 GEO 数据进行生物信息学分析，并对卵巢癌样本进行分析。结果表明，枢纽基因 KIF23 主要与细胞周期有关，并与预后不良呈正相关。同时，miR-424-5p 和 miR-503-5p 直接靶向 KIF23 的 3'UTR，抑制 KIF23 的表达，抑制卵巢癌细胞的增殖和迁移。此外，我们发现 miR-424/503 簇被启动子区域的高甲基化所抑制，这直接调节了 KIF23 的表达，从而提高了癌细胞在体外的致癌性能。总之，我们的研究证明了 miR-424/503 簇被 DNA 高甲基化沉默，从而促进了 KIF23 的表达，进而调节了卵巢癌细胞的增殖和迁移。干预这一过程可能是癌症治疗的一种新方法。
