Role of mitochondrial ribosomal proteins in bladder cancer
10.12483/j.issn.1009-8291.2026.04.013
- VernacularTitle:线粒体核糖体蛋白基因在膀胱癌中作用的初步研究
- Author:
Sheng FENG
1
;
Kaiyu QIAN
2
;
Xinghuan WANG
2
Author Information
1. Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071
2. Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071; Hubei Key Laboratory of Urological Diseases, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
- Publication Type:Journal Article
- Keywords:
bladder cancer;
mitochondrial ribosomal protein L12;
proliferation;
cell cycle arrest;
reactive oxygen species
- From:
Journal of Modern Urology
2026;31(4):366-375
- CountryChina
- Language:Chinese
-
Abstract:
Objective Mitochondrial ribosomal proteins(MRPs)that may affect bladder cancer cell proliferation were screened out through bioinformatics analysis. The relevant mechanism of pathogenesis of bladder cancer was explored and verified with clinical samples, cell experiments and functional experiments. Methods Differentially expressed genes(DEGs)in bladder cancer were identified through differential analysis of RNA-seq data downloaded from The Cancer Genome Atlas(TCGA)database. Subsequently, the intersection of these DEGs with MRPs was obtained to screen out MRPs differentially expressed in bladder cancer. Through survival analysis, MRPs possessing both prognostic value and differential expression were identified, and used as the objects of subsequent research. The relative expressions of MRPs were verified using 33 bladder cancer samples from Zhongnan Hospital of Wuhan University. Bladder cancer cells(T24 and UM-UC-3)were transfected with small interfering RNA(siRNA)and plasmids to achieve gene knockdown and overexpression. Changes in the proliferative capacity of bladder cancer cells following knockdown of the genes identified in survival analysis and simultaneous overexpression of cyclin D1(CCND1)were analyzed with 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT)assay and colony formation assay. The cell cycle status and reactive oxygen species(ROS)level were detected with flow cytometry. The efficiency of gene knockdown or overexpression, as well as changes in the expression of cell cycle-related proteins were verified with quantitative real-time polymerase chain reaction(qRT-PCR)and Western blotting. Results MRPL12 was screened out through bioinformatics and prognosis analysis, which was highly expressed in bladder cancer cells and correlated with poor prognosis. GSEA analysis suggested its association with oxidative phosphorylation, MYC and E2F pathways. When MRPL12 was knocked down, the proliferation of bladder cancer cells weakened and G1 phase arrest occurred. Western blotting showed that the expression of CCND1 and cyclin dependent kinase 4(CDK4)decreased after MRPL12 knockdown. In contrast, overexpression of CCND1 partially rescued the decreased proliferative capacity caused by MRPL12 knockdown and alleviated the G1 phase arrest of cells. Additionally, the ROS level in bladder cancer cells increased when MRPL12 was knocked down. Conclusion MRPL12 is highly expressed in bladder cancer cells and may affect cell proliferation through the cell cycle and mitochondrial function, showing potential application prospects.
