摘要
目的 通过研究敲减跨膜蛋白16A(TMEM16A)对卵巢癌增殖迁移及生存率的影响,并初步探讨其抑制卵巢癌的作用机制。方法 从The Cancer Genome Atlas(TCGA)数据库中下载卵巢癌的基因转录数据及临床信息,根据TMEM16A和信号传导及转录激活蛋白3(STAT3)表达的中位值将患者分为高表达组和低表达组,应用Kaplan-Meier法进行生存分析。将卵巢癌SKOV3细胞分为阴性对照组[转染空载质粒(scrambled shRNA)]和敲减组[转染靶向TMEM16A特异性shRNA(TMEM16A shRNA)]。用细胞计数试剂盒-8法检测细胞增殖情况,用细胞划痕实验检测细胞迁移能力,用蛋白质印迹法检测细胞TMEM16A和STAT3蛋白的表达情况。结果 Kaplan-Meier生存分析显示TMEM16A高表达卵巢癌患者预后生存期显著降低,STAT3高表达卵巢癌患者预后生存期显著降低,TMEM16A与STAT3共同高表达组总生存显著低于共同低表达组,差异均有统计学意义(均P<0.05)。卵巢癌SKOV3细胞阴性对照组和敲减组的细胞增殖率分别为(100.00±0)%和(54.12±4.01)%,迁移率分别为(84.89±0.04)%和(47.18±0.02)%,TMEM16A蛋白表达水平分别为0.79±0.12和0.11±0.08,磷酸化STAT3蛋白表达水平分别为0.69±0.09和0.18±0.06。阴性对照组的上述指标与敲减组比较,差异均有统计学意义(均P<0.05),说明敲减TMEM16A后磷酸化STAT3蛋白表达水平降低。结论 敲减TMEM16A激活STAT3信号通路可以抑制卵巢癌SKOV3细胞的增殖和迁移。
Objective By studying the effect of knockdown transmembrane protein 16 A(TMEM16 A) on the proliferation, migration and overall survival rate of ovarian cancer, the mechanism of its inhibition of ovarian cancer is preliminarily explored. Methods The gene transcription data and clinical information of ovarian cancer were downloaded from The Cancer Genome Atlas(TCGA) database. The patients were divided into high expression group and low expression group according to the median expression of TMEM16A and Signal transduction and the expression of activator of transcription 3(STAT3), and Kaplan-Meier method was used for survival analysis.Ovarian cancer SKOV3 cells were[ transfected with empty plasmid(scrambled shRNA) ]as negative control group, and[ transfected with TMEM16 A-specific shRNA( TMEM16A shRNA) ]as knockdown group. Western blot was used to detect the expression of TMEM16A in ovarian cancer SKOV3 cells after knockdown of TMEM16A. The proliferation ability of ovarian cancer SKOV3 cells was detected by CCK-8 cell proliferation assay. The migration ability of ovarian cancer cells was detected by cell migration assay. Western blot was used to detect the expression of STAT3 and TMEM16A in ovarian cancer SKOV3 cells.Results Kaplan-Meier survival analysis showed that the prognosis and survival time of ovarian cancer patients with high TMEM16A expression was significantly decreased,and the prognosis and survival time of ovarian cancer patients with high STAT3 expression was significantly reduced,and the overall survival of the co-high expression group of TMEM16A and STAT3 was significantly lower than that of the co-low expression group,statistical significance( all P < 0. 05). The cell proliferation rates of SKOV3 ovarian cancer cells in the negative control group and knockdown group were( 100. 00 ± 0) % and( 54. 12 ± 4. 01) %;the migration rates were( 84. 89 ± 0. 04) % and( 47. 18 ± 0. 02) %;the TMEM16A protein expression levels were 0. 79 ± 0. 12 and 0. 11 ± 0. 08;the protein expression levels of phosphorylate
作者
梁林林
孙静莉
LIANG Lin-lin;SUN Jing-li(Department of Obstetrics Gynecology,General Hospital of Northern Theatre Command,Shenyang 110122,Liaoning Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2022年第15期1774-1777,共4页
The Chinese Journal of Clinical Pharmacology
基金
国家重点研发计划“精准医学研究”专项基金资助项目(2018-22-3)。
关键词
卵巢癌
跨膜蛋白16A
生存分析
信号传导及转录激活蛋白3
ovarian cancer
transmembrane protein 16A
survival analysis
signal transduction and the expression of activator of transcription 3
