Upregulated WDR5 promotes proliferation, self-renewal and chemoresistance in bladder cancer via mediating H3K4 trimethylation

Xu Chen; Weibin Xie; Peng Gu; Qingqing Cai; Bo Wang; Yun Xie; Wen Dong; Wang He; Guangzheng Zhong; Tianxin Lin; Jian Huang

doi:10.1038/srep08293

Upregulated WDR5 promotes proliferation, self-renewal and chemoresistance in bladder cancer via mediating H3K4 trimethylation

Sci Rep. 2015 Feb 6:5:8293. doi: 10.1038/srep08293.

Authors

Xu Chen¹, Weibin Xie¹, Peng Gu¹, Qingqing Cai², Bo Wang¹, Yun Xie³, Wen Dong³, Wang He³, Guangzheng Zhong³, Tianxin Lin¹, Jian Huang³

Affiliations

¹ 1] Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China [2] Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
² Department of Internal Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
³ Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Aged, 80 and over
Animals
Antineoplastic Agents / pharmacology
Case-Control Studies
Cell Cycle Checkpoints / genetics
Cell Line, Tumor
Cell Proliferation
Cell Self Renewal* / genetics
Cell Transformation, Neoplastic / genetics
Cell Transformation, Neoplastic / metabolism
Cisplatin / pharmacology
Disease Models, Animal
Drug Resistance, Neoplasm* / genetics
Female
Gene Knockdown Techniques
Histone-Lysine N-Methyltransferase / genetics
Histone-Lysine N-Methyltransferase / metabolism*
Histones / metabolism*
Humans
Immunohistochemistry
Intracellular Signaling Peptides and Proteins
Lymphatic Metastasis
Male
Methylation
Middle Aged
Neoplasm Grading
Neoplasm Staging
Tumor Burden
Urinary Bladder Neoplasms / genetics
Urinary Bladder Neoplasms / metabolism*
Urinary Bladder Neoplasms / pathology

Substances

Antineoplastic Agents
Histones
Intracellular Signaling Peptides and Proteins
WDR5 protein, human
Histone-Lysine N-Methyltransferase
Cisplatin