细胞周期相关蛋白CENPF促进卵巢癌细胞的恶性行为研究  

Cell cycle-related protein CENPF promotes malignant behavior of ovarian cancer cells

作　　者：刘欣悦 张维娜[1] 郭丽[1] 汤心慧 赵天南 张裕民 张萍[1] Liu Xinyue;Zhang Weina;Guo Li;Tang Xinhui;Zhao Tiannan;Zhang Yumin;Zhang Ping(Department of Gynecology,Qingdao Municipal Hospital,Qingdao Shandong 266000;Graduate School,Dalian Medical University,Dalian Liaoning 116000;Department of Gynecology,People’s Hospital of Changzhi,Changzhi Shanxi 046000;Institute of Biological Testing,Heze Institute for Food and Drug Testing,Heze Shandong 274000,P.R.China)

机构地区：[1]青岛市市立医院妇科,山东青岛266000 [2]大连医科大学研究生院,辽宁大连116000 [3]长治市人民医院妇科,山西长治046000 [4]菏泽市食品药品检验检测研究院生物检测研究所,山东菏泽274000

出　　处：《中国计划生育和妇产科》2022年第10期89-93,I0004,共6页Chinese Journal of Family Planning & Gynecotokology

基　　金：山东省医药卫生科技发展计划项目(项目编号:202105010641)。

摘　　要：目的筛选卵巢癌中细胞周期相关核心靶点并研究其在卵巢癌发生发展中的功能和分子机制。方法通过在GEO数据库中搜索和整合细胞周期相关基因,结合TCGA数据库找到核心作用靶点即目的基因,Kaplan-Meier图的微阵列数据用于验证该靶点与生存是否相关。然后通过蛋白质印迹验证沉默目的基因的表达,利用CCK-8法检测细胞活力,流式细胞术检测细胞周期分布,细胞划痕和Transwell实验检测细胞的迁移和侵袭能力。分析沉默目的基因后所参与的信号通路,通过蛋白质印迹从而验证该目的基因潜在的分子机制。结果CENPF在卵巢癌组织中表达明显上调,高CENPF mRNA表达与较差的生存率和较短的无进展生存期相关。蛋白质印迹验证CENPF在卵巢癌细胞中上调。功能实验表明,沉默CENPF可以抑制细胞增殖、侵袭、迁移以及阻滞细胞周期于G2/M期,且抑制PI3K、p-AKT/AKT、p-mTOR/mTOR的表达(P<0.05)。结论细胞周期相关蛋白CENPF可能通过PI3K/AKT/mTOR促进卵巢癌细胞的恶性行为。Objective To screen cell cycle-related core targets in ovarian cancer and study their functions and molecular mechanisms in the occurrence and development of ovarian cancer.Methods By searching and integrating cell cycle-related genes in the GEO database,combined with the TCGA database to find the core target gene,the microarray data of the Kaplan-Meier plot was used to verify whether the target was related to survival.Then the expression of silenced target gene was verified by western blotting,cell viability was detected by CCK-8 method,cell cycle distribution was detected by flow cytometry,and cell migration and invasion ability were detected by cell scratch and Transwell assay.The signaling pathways involved in silencing the target gene were analyzed,and the potential molecular mechanism of the target gene was verified by western blotting.Results CENPF expression was significantly up-regulated in ovarian cancer tissues,and high CENPF mRNA expression was associated with poorer survival and shorter progression-free survival.The upregulation of CENPF in ovarian cancer cells was verified by western blotting.Functional experiments showed that silencing CENPF could inhibit cell proliferation,invasion,migration and arrest the cell cycle in G2/M phase,and inhibit the expression of PI3 K,p-AKT/AKT,and p-mTOR/mTOR(P<0.05).Conclusion The cell cycle-related protein CENPF may promote the malignant behavior of ovarian cancer cells through PI3 K/AKT/mTOR.

关 键 词：卵巢癌 细胞周期 着丝粒蛋白F(CENPF) PI3K/AKT/mTOR信号通路 

分 类 号：R737.31[医药卫生—肿瘤]