Gene Expression and Regulatory Webwork of POLR2K in Bladder Carcinogenesis by Integrated Bioinformatics Approaches

Abstract

Background：RNA polymerase II subunit K (POLR2K) belongs to one of the multiple subunits of RNA polymerase II (Pol II), whose biological function is to synthesize mRNA. Aberrant POLR2K expression is related to carcinogenesis. However, POLR2K’s underlying role in bladder cancer has not been explored. In the current study, we intend to analyze the function of POLR2K and its regulatory network within bladder cancer.Methods: Public sequencing data was obtained from GEO and TCGA to investigate POLR2K expression and regulatory network within bladder cancer (BLCA) by using GEPIA and Oncomine as well as cBioPortal online tool. LinkedOmics was employed to identify genes displaying significantly differential expression patterns and to perform GO and KEGG analyses. After differential genes was assigned and ranked, GSEA analyses was performed to obtain target networks for transcription factors, miRNAs, and kinases that could regulate POLR2K–associated gene network. Subsequent functional webwork analyses were used to identify cancer-relevant pathways Moreover, POLR2K gene is verified, by ChIP-seq in MCF-7 cell line , with transcription factor binding evidence in the ENCODE Transcription Factor Binding Site Profiles dataset.Conclusions: The current study implies that POLR2K gene is overexpressed and often amplified in BLCA, providing the first evidence that POLR2K deregulation, in particular increased transcription, may promote BLCA. These findings uncover a unique expression patterns of POLR2K and its potential regulatory networks in BLCA, contributing greatly to study of the role of POLR2K in cancer development.

Deregulations of RNA Pol II Subunits in Cancer

“…Finally, in bladder cancer patients, high levels of POLR2K were associated with poor progression free and overall survival. Furthermore, the knock down of the Pol II subunit reduced the viability of two bladder cancer cell lines, indicating that its decreased expression could slow down cell growth [149].…”