基础医学与临床 ›› 2019, Vol. 39 ›› Issue (8): 1168-1174.

• 研究论文 • 上一篇    下一篇

核糖体蛋白25(RPS25)通过调节c-Myc促进肾透明细胞癌的发生发展

杨航1,杨晶欣2,郑兰兰3,胡作为1,关江锋1,王兵1,覃双来1   

  1. 1. 华中科技大学同济医学院附属中西医结合医院
    2. 中国人民解放军第161医院
    3. 湖北医药学院
  • 收稿日期:2018-11-28 修回日期:2019-03-30 出版日期:2019-08-05 发布日期:2019-07-16
  • 通讯作者: 杨晶欣 E-mail:173882842@qq.com
  • 基金资助:
    TOP1通过泛素化连接酶APC/C调节肿瘤对喜数碱耐受的作用机制研究

Ribosomal protein 25(RPS25) promotes the development of renal transparent cell carcinoma through regulating c-Myc

  • Received:2018-11-28 Revised:2019-03-30 Online:2019-08-05 Published:2019-07-16

摘要: 目的 探讨核糖体蛋白25(RPS25)基因在肾透明细胞癌(ccRCC)中的作用。方法 利用定量PCR、Western blot和双荧光素酶报告系统检测RPS25基因在ccRCC组织和肾癌细胞系中的表达以及c-Myc基因启动子活性;通过MTS实验和Transwell实验研究RPS25及其下游基因的过表达或干扰对肾癌细胞的增殖、迁移和侵袭等功能的影响;利用Kaplan-Meier法分析TCGA数据库中ccRCC患者中RPS25的表达与预后的关系。结果 定量PCR检测发现RPS25在肾癌细胞系和ccRCC组织中的表达上调(p<0.05)。RPS25的下调可抑制肾癌细胞的增殖、迁移和侵袭(p<0.001)。在肾癌细胞中过表达RPS25可通过翻译和转录途径增加c-Myc的表达,且共表达c-Myc能够降低由RPS25干扰导致的肿瘤抑制作用(p<0.01)。Kaplan-Meier 曲线显示RPS25的高表达与ccRCC患者的不良预后相关(p<0.01)。结论 RPS25作为一个癌基因在ccRCC中发挥功能,对ccRCC的临床诊疗和预后评估具有重要价值。

关键词: RPS25,c-Myc,肾透明细胞癌

Abstract: Objective To investigate the effects of ribosomal protein 25 (RPS25) on development and progression of ccRCC. Methods Quantitative Real-time PCR (qPCR), Western blot analysis, and dual luciferase reporter gene assays were conducted to examine RPS25 expression and c-Myc promoter activity in renal cancer tissue and renal cancer cell lines. Proliferation, migration and invasion of renal cancer cells either exhibiting knockdown of RPS25 or its downstream gene c-Myc were assessed by MTS and Transwell assay. Kaplan-Meier Plotter was used to analyze the survival of ccRCC patients with different RPS25 levels using data from The Cancer Genome Atlas consortia (TCGA). Results qPCR results showed that RPS25 mRNA was significantly increased in renal cancer cell lines and ccRCC samples. Mechanistic studies demonstrated that RPS25 promoted c-Myc expression by both translational control and transcription mechanisms. Particularly, coexpression of c-Myc reversed the depletion of RPS25-mediated tumor suppression. Kaplan-Meier Plotter showed that the increased RPS25 level correlated with poor survival. Conclusion This study demonstrates that RPS25 as an oncogene hae therapeutic potential and clinical values as a prognostic factor in ccRCC.

Key words: RPS25,c-Myc,clear cell renal cell carcinoma