Abstract
WD repeat domain 5 (WDR5) plays an important role in various biological functions through the epigenetic regulation of gene transcription; however, its role in bladder cancer remains largely unknown. Our study investigated the role of WDR5 in bladder cancer and demonstrated that WDR5 was upregulated in bladder cancer tissues, and elevated WDR5 protein levels positively correlated with advanced tumor stage and poor survival. Through gain or loss of function, we demonstrated that WDR5 promoted proliferation, self-renewal and chemoresistance to cisplatin in bladder cancer cells in vitro, and tumor growth in vivo. Mechanistically, WDR5 regulated various functions in bladder cancer by mediating the transcription of cyclin B1, cyclin E1, cyclin E2, UHMK1, MCL1, BIRC3 and Nanog by histone H3 lysine 4 trimethylation. Therefore, we have discovered that WDR5 plays an important role in bladder cancer suggesting that WDR5 is a potential biomarker and a promising target in the treatment of bladder cancer.
Highlights
WD repeat domain 5 (WDR5) plays an important role in various biological functions through the epigenetic regulation of gene transcription; its role in bladder cancer remains largely unknown
Our study investigated the role of WDR5 in bladder cancer and demonstrated that WDR5 was upregulated in bladder cancer tissues, and elevated WDR5 protein levels positively correlated with advanced tumor stage and poor survival
The Polycomb repression complex 2 (PRC2) mediates histone H3 lysine 27 trimethylation (H3K27me3), which is correlated with gene repression, whereas the MLL/SET1 complexes mediates H3K4 methylation, which is correlated with gene activation[8]
Summary
WD repeat domain 5 (WDR5) plays an important role in various biological functions through the epigenetic regulation of gene transcription; its role in bladder cancer remains largely unknown. Through gain or loss of function, we demonstrated that WDR5 promoted proliferation, self-renewal and chemoresistance to cisplatin in bladder cancer cells in vitro, and tumor growth in vivo. The present study reveals that WDR5 plays a critical role in embryonic stem cell self-renewal by interacting with Oct[4] and mediating H3K4 methylation[11]. We found that WDR5 expression was increased in bladder cancer tissues and correlated with advanced tumor stage and poor survival. WDR5 promoted bladder cell proliferation, self-renewal and chemoresistance to cisplatin in vitro, and accelerated tumor growth in vivo. We identified some target genes of WDR5 by microarray and chromatin immunoprecipitation (ChIP) qPCR
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