Wang Jieyu, Jia Nan, Lyv Tianjiao, Wang Chao, Tao Xiang, Wong KwongKwok, Li Qin, Feng Weiwei
Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai, 200032, China.
Shanghai Key Laboratory of Female Reproductive Endocrine-Related Disease of Fudan University, Shanghai, 200011, China.
J Cancer. 2018 Sep 25;9(20):3743-3754. doi: 10.7150/jca.22418. eCollection 2018.
Human paired box 2 (PAX2) plays a key role in cell fate, early patterning and organogenesis. We investigated the function of PAX2 on the biological behavior of endometrial cancer in vitro and in vivo and to explore the regulation mechanism, stable knocking-down and over-expression PAX2 endometrial cancer cell lines were established. CCK-8 and transwell assays were applied to determine proliferation, invasion and migration ability. Cell cycle distribution was analyzed by flow cytometry. Affymetrix GeneChip® human Exon 1.0 ST arrays was used to screen the downstream target genes of PAX2. PAX2 significantly enhanced proliferation and invasiveness. In addition, PAX2 influenced the expression of cyclin-dependent kinase 1(CDK1), which play pivotal roles in cell cycle pathway. When CDK1 was knocked down, and the cell proliferation promotion role of PAX2 was attenuated dramatically to a level comparable with the control groups. PAX2, though influencing the expression of CDK1, promotes the proliferation, enhances the mobility of endometrial cancer cells, thus exerts an important role in the carcinogenesis of endometrial cancer. PAX2 may be a potential therapeutic target for endometrial cancer.
人类配对盒基因2（PAX2）在细胞命运、早期模式形成和器官发生中起关键作用。我们在体外和体内研究了PAX2对子宫内膜癌生物学行为的作用，并探索其调控机制，建立了稳定敲低和过表达PAX2的子宫内膜癌细胞系。应用CCK-8和Transwell实验检测细胞的增殖、侵袭和迁移能力。通过流式细胞术分析细胞周期分布。使用Affymetrix GeneChip®人类外显子1.0 ST阵列筛选PAX2的下游靶基因。PAX2显著增强细胞增殖和侵袭能力。此外，PAX2影响细胞周期蛋白依赖性激酶1（CDK1）的表达，CDK1在细胞周期途径中起关键作用。当敲低CDK1时，PAX2促进细胞增殖的作用显著减弱至与对照组相当的水平。PAX2虽然影响CDK1的表达，但可促进子宫内膜癌细胞的增殖，增强其迁移能力，从而在子宫内膜癌的发生发展中发挥重要作用。PAX2可能是子宫内膜癌潜在的治疗靶点。
