Oncogenesis ( IF 6.2 ) Pub Date : 2023-10-02 , DOI: 10.1038/s41389-023-00493-z Guoli Wang 1, 2 , Xin He 2 , Huiqi Dai 1, 2 , Lingyi Lin 1, 2 , Wenmin Cao 2 , Yao Fu 3 , Wenli Diao 2 , Meng Ding 2 , Qing Zhang 2 , Wei Chen 1, 2 , Hongqian Guo 1, 2
Lymph node (LN) metastasis is one of the key prognostic factors in bladder cancer, but its underlying mechanisms remain unclear. Here, we found that elevated expression of WD repeat domain 4 (WDR4) in bladder cancer correlated with worse prognosis. WDR4 can promote the LN metastasis and proliferation of bladder cancer cells. Mechanistic studies showed that WDR4 can promote the nuclear localization of DEAD-box helicase 20 (DDX20) and act as an adaptor to bind DDX20 and Early growth response 1 (Egr1), thereby inhibiting Egr1-promoted transcriptional expression of arrestin beta 2 (ARRB2) and ultimately contributing to the progression of bladder cancer. Immunohistochemical analysis confirmed that WDR4 expression is also an independent predictor of LN metastasis in bladder cancer. Our results reveal a novel mechanism of LN metastasis and progression in bladder cancer and identify WDR4 as a potential therapeutic target for metastatic bladder cancer.
中文翻译:
WDR4通过ARRB2转录下调促进膀胱癌的进展和淋巴转移
淋巴结(LN)转移是膀胱癌的关键预后因素之一,但其潜在机制仍不清楚。在这里,我们发现膀胱癌中 WD 重复结构域 4 (WDR4) 的表达升高与预后较差相关。WDR4可以促进膀胱癌细胞的淋巴结转移和增殖。机制研究表明,WDR4可以促进DEAD-box解旋酶20(DDX20)的核定位,并作为接头结合DDX20和早期生长反应1(Egr1),从而抑制Egr1促进的视紫红质抑制蛋白β2(ARRB2)的转录表达最终导致膀胱癌的进展。免疫组织化学分析证实,WDR4 表达也是膀胱癌 LN 转移的独立预测因子。我们的结果揭示了膀胱癌淋巴结转移和进展的新机制,并将 WDR4 确定为转移性膀胱癌的潜在治疗靶点。