TMEM45A在肾透明细胞癌中的表达及作用机制研究

doi:10.11904/j.issn.1002-3070.2019.04.006

摘要/Abstract

摘要： 目的探讨TMEM45A(Transmembrane protein 45A,TMEM45A)在肾透明细胞癌(Clear cell renal cell carcinoma,ccRCC)中的表达及作用。方法利用R语言提取Oncomine数据库中TMEM45A相关研究的数据;利用GEPIA数据库在线分析TMEM45A表达水平与肾透明细胞癌分期及生存时间的关系;实时定量PCR和Western blot检测TMEM45A在肾透明细胞癌组织及肾癌细胞系中的表达;应用针对TMEM45A的siRNA转染Caki-1细胞后,实时定量PCR和Western blot验证TMEM45A表达降低,CCK8分析抑制TMEM45A表达后对细胞增殖的影响,实时定量PCR和Western blot分析低表达TMEM45A抑制细胞增殖的作用机制。结果 Oncomine数据库中共收集了384项TMEM45A相关的研究,35项有统计学差异,其中25项表达升高、10项表达降低。有4项研究与ccRCC相关,共有115例样本。分析发现,ccRCC中TMEM45A表达显著升高(P＜0.05);同时发现高表达的TMEM45A与ccRCC高分期及预后不良密切相关(P＜0.05)。与正常的肾脏组织相比,TMEM45A mRNA在肾透明细胞癌组织中表达明显升高(P＜0.05)。人肾癌Caki-1和786-0细胞中TMEM45A mRNA和蛋白表达高于正常肾小管上皮HK-2细胞。TMEM45A siRNA转染Caki-1细胞48 h、72 h后,细胞的增殖能力显著下降(P＜0.001)。同时发现抑制TMEM45A后,PCNA和Cyclin D1蛋白和mRNA表达明显下降(P＜0.05)。结论 TMEM45A在ccRCC中表达升高且与ccRCC分期、预后相关,可能通过调控PCNA和Cyclin D1参与肾癌细胞的增殖。

关键词: 肾透明细胞癌, TMEM45A, Oncomine数据库, GEPIA数据库, 细胞增殖

Abstract: Objective The Objective of this study was to investigate the expression and function of TMEM45A(transmembrane protein 45A)in clear cell renal cell carcinoma(ccRCC).Methods The data of TMEM45A in Oncomine database were extracted by R language.The relationship between the expression level of TMEM45A and the stage or survival time of ccRCC was analyzed by GEPIA database.qRT-PCR and Western blot were used to detect the expression of TMEM45A in ccRCC tissues and renal cell carcinoma cell lines.After transfection of TMEM45A siRNA,the low expression ofTMEM45A in Caki-1 cells was confirmed by qRT-PCR and Western blot.Cell proliferation after knockdown TMEM45A was analyzed in Caki-1 cells by CCK8.The mechanism of action in the low expression of TMEM45A inhibited cell proliferation was analyzed in Caki-1 cells by qRT-PCR and Western blot.Results A total of 384 TMEM45A-related studies were collected in the Oncomine database,with 35 statistically significant differences,25 of them elevated and 10 decreased.Four studies were associated with ccRCC with a total of 115 samples.The expression of TMEM45A was significantly increased in ccRCC(P＜0.05).It was also found that the high expression of TMEM45A was closely associated with high ccRCC stage and poor prognosis(P＜0.05).When compared with the normal kidney tissues,TMEM45A mRNA was significantly increased in ccRCC tissues(P＜0.05).The expression of TMEM45A at levels of mRNA and protein in Caki-1 and 786-0 cells was higher than that in normal renal tubular epithelial HK-2 cells.After transfection with TMEM45A siRNA for 48h and 72h,the proliferation of Caki-1 cells was significantly decreased(P＜0.001).At the same time,it was found that the expression of PCNA and cyclin D1 at levels of mRNA and protein was significantly decreased(P＜0.05).Conclusion The expression of TMEM45A is elevated in ccRCC and is associated with ccRCC staging and prognosis.It may be involved in the proliferation of renal carcinoma cells by regulating PCNA and Cyclin D1.

Key words: Clear cell renal cell carcinoma, TMEM45A, Oncomine database, GEPIA database, Proliferation

中图分类号:

R737.11

闫若东, 任山, 隋文印, 朴仁京. TMEM45A在肾透明细胞癌中的表达及作用机制研究[J]. 实用肿瘤学杂志, 2019, 33(4): 317-322.

YAN Ruodong, REN Shan, SUI Wenyin, PIAO Renjing. Expression and mechanism of TMEM45A in renal clear cell carcinoma[J]. Journal of Practical Oncology, 2019, 33(4): 317-322.

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