title: Upregulated WDR5 promotes proliferation, self-renewal and chemoresistance in bladder cancer via mediating H3K4 trimethylation.
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.
authors: 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.
authors: Xu
authors: X
authors: Chen
authors: 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.
authors: Weibin
authors: W
authors: Xie
authors: 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.
authors: Peng
authors: P
authors: Gu
authors: Department of Internal Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors: Qingqing
authors: Q
authors: Cai
authors: 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.
authors: Bo
authors: B
authors: Wang
authors: Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors: Yun
authors: Y
authors: Xie
authors: Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors: Wen
authors: W
authors: Dong
authors: Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors: Wang
authors: W
authors: He
authors: Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors: Guangzheng
authors: G
authors: Zhong
authors: 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.
authors: Tianxin
authors: T
authors: Lin
authors: Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors: Jian
authors: J
authors: Huang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D016022:Case-Control Studies; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000066673:Cell Self Renewal / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D055785:Gene Knockdown Techniques; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D008207:Lymphatic Metastasis; D008297:Male; D008745:Methylation; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D047368:Tumor Burden; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; C502547:WDR5 protein, human; D011495:Histone-Lysine N-Methyltransferase; D002945:Cisplatin
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