Research Paper Volume 12, Issue 9 pp 8728—8741

High PRMT5 expression is associated with poor overall survival and tumor progression in bladder cancer

Lei Tan 1, 2, 3, *, , Kanghua Xiao 2, 3, *, , Yunlin Ye 2, 3, *, , Haitao Liang 2, 3, , Mingkun Chen 4, , Junhang Luo 1, , Zike Qin 2, 3, ,

  • 1 Department of Urology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
  • 2 State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
  • 3 Department of Urology, Sun Yat-Sen University Cancer Center, Guangzhou, China
  • 4 Department of Urology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China
* Equal contribution

received: December 6, 2019 ; accepted: March 30, 2020 ; published: May 11, 2020 ;

https://doi.org/10.18632/aging.103198
How to Cite

Copyright © 2020 Tan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Arginine methyltransferase 5 (PRMT5) is involved in a variety of cancers. We used bioinformatics analysis to investigate PRMT5 overexpression in bladder urothelial cancer (BUC) and its clinical significance. We also conducted molecular biology experiments to investigate the effect of PRMT5 on the phenotype of BUC cells in vitro and in vivo. PRMT5 was found to be upregulated in BUC tissue in the Oncomine and The Cancer Genome Atlas databases. We validated the results from these databases in a cohort of BUC samples. Kaplan-Meier and Cox multivariate analyses demonstrated that PRMT5 upregulation is an independent prognostic risk factor for BUC. The in vitro and in vivo phenotypic experiments found that downregulated expression of PRMT5 in BUC cells inhibits BUC cell proliferation and aggression. In addition, gene set enrichment analysis demonstrated that PRMT5 knockdown leads to cell cycle G1/S arrest, deactivation of Akt, and mTOR phosphorylation in BUC cells. These results suggest that PRMT5 could be used as a potential molecular marker for BUC in the future.

Abbreviations

BUC: bladder urothelial cancer; NMIBC: non–muscle-invasive bladder cancer; MIBC: muscle-invasive bladder cancer; PRMT5: protein arginine methyltransferase 5; TCGA: The Cancer Genome Atlas; qRT-PCR: quantitative real-time polymerase chain reaction analysis; Rb: retinoblastoma; CCK-8: cell counting kit-8 assay; EdU: 5-ethynyl-20-deoxyuridine; siRNA: small interference RNA; shRNA: short hairpin RNA.