Upregulated WDR5 promotes proliferation, self-renewal and chemoresistance in bladder cancer via mediating H3K4 trimethylation
Upregulated WDR5 promotes proliferation, self-renewal and chemoresistance in bladder cancer via mediating H3K4 trimethylation
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WDR5 上调通过介导 H3K4 三甲基化促进膀胱癌的增殖、自我更新和化疗耐药
DOI：
10.1038/srep08293
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发表时间：
2015-02-06
影响因子：
4.6
通讯作者：
Huang, Jian
中科院分区：
文献类型：
--
作者：
Chen, Xu;Xie, Weibin;Huang, Jian
WD重复结构域5(WDR5)通过基因转录的表观遗传调控在多种生物学功能中发挥重要作用，但其在膀胱癌中的作用仍不清楚。本研究探讨了WDR5在膀胱癌中的作用，发现WDR5在膀胱癌组织中表达上调，且WDR5蛋白表达水平升高与膀胱癌分期和预后呈正相关。通过功能的获得或丧失，我们证明了WDR5在体外和体内促进了膀胱癌细胞的增殖、自我更新和对顺铂的化疗耐药性。在机制上，WDR5通过组蛋白H3赖氨酸4的三甲基化调控细胞周期蛋白B1、细胞周期蛋白E1、细胞周期蛋白E2、UHMK1、MCL1、BIRC3和Nanog的转录，从而调控膀胱癌的多种功能。因此，我们发现WDR5在膀胱癌中起着重要的作用，提示WDR5在膀胱癌的治疗中是一个潜在的生物标志物和有希望的靶点。
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 cellsin vitroand tumor growthin 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.