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

Lei Tan,Kanghua Xiao,Haitao Liang,Yunlin Ye,Junhang Luo,Zike Qin,Mingkun Chen

doi:10.18632/aging.103198

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.

Highlights

Bladder urothelial cancer (BUC) is one of the most common genitourinary carcinomas in China [1]
We performed bioinformatics analysis in three BUC data sets from the Oncomine database and found that Protein arginine methyltransferase 5 (PRMT5) was upregulated in superficial or infiltrating BUC tissue compared with nontumor bladder tissues (Figure 1A–1D)
On further bioinformatics analysis using The Cancer Genome Atlas (TCGA) database, we confirmed that PRMT5 expression was higher in BUC tissue than in matched nonneoplastic bladder tissue (Figure 1E)

Summary

Introduction

Bladder urothelial cancer (BUC) is one of the most common genitourinary carcinomas in China [1]. It is a significant cause of mortality in Western countries [2, 3]. BUC is categorized as muscle-invasive bladder cancer (MIBC) and non–muscle-invasive bladder cancer (NMIBC). Most studies on the etiology of BUC have focused on genetic transformation. Many oncogenes, such as C-myc [6], Bcl-2 [7], FGFR3 [8], and c-erbB-2 [9], have been found to be associated with BUC prognosis and progression [10]. The development of BUC is a complicated pathological process that requires further study

Methods

Results

Conclusion