跨膜蛋白16F通过上调细胞周期蛋白D1的表达促进卵巢癌细胞增殖和侵袭的研究

Transmembrane protein 16F promotes the proliferation and invasion of ovarian cancer cells by up-regulating the expression of Cyclin D1

目的 研究跨膜蛋白16F(TMEM16F)对卵巢癌患者预后的影响。方法 从公共数据库癌症基因组图谱(TCGA)在线数据库中下载卵巢癌的临床及转录组数据,根据TMEM16F基因表达的中位值将患者分为高表达组和低表达组,用Kaplan-Meier法进行生存分析。用Western blot法检测过表达及敲减TMEM16F后卵巢癌SKOV3细胞中细胞周期蛋白1(CCND1)的表达情况。用CCK-8实验法检测卵巢癌SKOV3细胞转染过表达TMEM16F质粒及用CCND1抑制药处理后的细胞增殖能力。用Transwell侵袭实验检测过表达及敲减TMEM16F后卵巢癌SKOV3细胞的转移情况。结果 Kaplan-Meier生存分析显示:TMEM16F高表达卵巢癌患者的预后生存期显著降低(42.63%vs 49.43%,P<0.01),TMEM16F与CCND1联合高表达组的总生存显著低于共同低表达组(41.63%vs 52.63%,P<0.01)。过表达TMEM16F上调CCND1蛋白表达,反之敲减TMEM16F后CCND1蛋白表达水平降低。过表达TMEM16F后,卵巢癌SKOV3细胞的增殖能力增强,加入CCND1抑制药后可逆转其增强的细胞增殖能力。TMEM16F高表达能增强卵巢癌SKOV3细胞的侵袭能力。结论 TMEM16F通过激活CCND1促进卵巢癌SKOV3细胞的增殖和侵袭。

Objective To study the effect of transmembrane protein 16 F(TMEM16 F)on the prognosis of patients with ovarian cancer. Methods The clinical data and transcriptome of ovarian cancer were downloaded from the public database Cancer Genome Atlas(TCGA)online database. According to the median value of TMEM16F expression, patients were divided into high expression group and low expression group. The Kaplan-Meier method was used for survival analysis. Western blot method was used to detect the expression of Cyclin D1(CCND1) protein in ovarian cancer SKOV3 cells after overexpression and knockdown of TMEM16F. CCK-8 cell proliferation experiment was used to detect the cell proliferation ability of ovarian cancer SKOV3 cells transfected with overexpressing TMEM16F plasmid and CCND1 inhibitor. Transwell invasion assay was used to detect the invasion of ovarian cancer SKOV3 cells after overexpression and knockdown of TMEM16F. Results Kaplan-Meier survival analysis showed that the prognostic survival of patients with ovarian cancer with high TMEM16F expression was significantly reduced.( 42. 63% vs 49. 43%,P < 0. 01) The overall survival of TMEM16F and CCND1 combined high expression group was significantly lower than that of common low expression group( 41. 63% vs 52. 63%,P < 0. 01).Overexpression of TMEM16F up-regulated the expression of CCND1 protein,on the contrary,the expression of CCND1protein decreased after knocking down TMEM16F. The cell proliferation ability of ovarian cancer SKOV3 cells was enhanced after overexpression of TMEM16F,and the enhanced cell proliferation ability could be reversed by adding CCND1 inhibitor. High expression of TMEM16F promoted the invasion ability of ovarian cancer SKOV3 cells.Conclusion TMEM16F promotes the proliferation and invasion of ovarian cancer SKOV3 cells by activating CCND1.