Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China.
Department of Central Sterile Supply, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, PR China.
Histol Histopathol. 2023 Aug;38(8):917-928. doi: 10.14670/HH-18-558. Epub 2022 Dec 2.
Bladder cancer is one of the most commonly diagnosed malignancies of the urinary system with relatively poor prognosis and insufficient treatment strategies. RFWD3 is an E3 ligase whose function is rarely investigated in malignant tumors.
A tissue microarray was used for evaluating RFWD3 expression in clinical samples and its correlation with tumor characteristics and patients' prognosis. RFWD3 knockdown and overexpression cell models were constructed for conducting loss-of-function and gain-of-function assays. qPCR and western blotting were used for detecting mRNA and protein levels of RFWD3, respectively. MTT assay, colony formation assay, flow cytometry, wound-healing assay and transwell assay were carried out to demonstrate the change of cell phenotypes upon RFWD3 knockdown.
RFWD3 expression was relatively higher in bladder cancer tissues than in normal tissues, which is correlated with higher N stage and poorer prognosis of patients. Knockdown of RFWD3 in bladder cancer cells significantly inhibited cell proliferation, colony formation, promote cell apoptosis and restrained cell migration. Overexpression of RFWD3 induced the opposite effects.
It was illustrated that RFWD3 possesses excellent tumor-promoting ability in bladder cancer. Accordingly, RFWD3 may be a promising therapeutic target in the targeted therapy of bladder cancer, which is worth further research.
膀胱癌是泌尿系统最常见的恶性肿瘤之一，预后相对较差，治疗策略不足。RFWD3 是一种 E3 连接酶，其在恶性肿瘤中的功能鲜少被研究。
采用组织微阵列评估 RFWD3 在临床样本中的表达及其与肿瘤特征和患者预后的相关性。构建 RFWD3 敲低和过表达细胞模型，进行功能丧失和功能获得实验。qPCR 和 Western blot 分别用于检测 RFWD3 的 mRNA 和蛋白水平。MTT 法、集落形成实验、流式细胞术、划痕愈合实验和 Transwell 实验用于检测 RFWD3 敲低后细胞表型的变化。
RFWD3 在膀胱癌组织中的表达高于正常组织，与患者的 N 分期较高和预后较差相关。膀胱癌细胞中 RFWD3 的敲低显著抑制细胞增殖、集落形成，促进细胞凋亡，抑制细胞迁移。过表达 RFWD3 则诱导相反的效应。
RFWD3 在膀胱癌中具有优异的促瘤能力。因此，RFWD3 可能是膀胱癌靶向治疗中有前途的治疗靶点，值得进一步研究。
