Chen Haotian, Wen Jing, Zhang Wentao, Ma Wenchao, Guo Yadong, Shen Liliang, Zhang Zhijin, Yang Fuhan, Zhang Yue, Gao Yaohui, Xu Tianyuan, Yan Yang, Li Wei, Zhang Junfeng, Mao Shiyu, Yao Xudong
Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, China.
iScience. 2024 Mar 29;27(4):109624. doi: 10.1016/j.isci.2024.109624. eCollection 2024 Apr 19.
Circular RNAs (circRNAs) play crucial biological functions in various tumors, including bladder cancer (BCa). However, the roles and underlying molecular mechanisms of circRNAs in the malignant proliferation of BCa are yet unknown. CircKDM1A was observed to be downregulated in BCa tissues and cells. Knockdown of circKDM1A promoted the proliferation of BCa cells and bladder xenograft growth, while the overexpression of circKDM1A exerts the opposite effect. The dual-luciferase reporter assay revealed that circKDM1A was directly bound to miR-889-3p, acting as its molecular sponge to downregulate CPEB3. In turn, the CPEB3 was bound to the CPE signal in p53 mRNA 3'UTR to stabilize its expression. Thus, circKDM1A-mediated CPEB3 downregulation inhibits the stability of p53 mRNA and promotes BCa malignant progression. In conclusion, circKDM1A functions as a tumor suppressor in the malignant proliferation of BCa via the miR-889-3p/CPEB3/p53 axis. CircKDM1A may be a potential prognostic biomarker and therapeutic target of BCa.
环状RNA(circRNAs)在包括膀胱癌(BCa)在内的多种肿瘤中发挥着关键的生物学功能。然而,circRNAs在BCa恶性增殖中的作用及潜在分子机制尚不清楚。研究发现,circKDM1A在BCa组织和细胞中表达下调。敲低circKDM1A可促进BCa细胞增殖和膀胱异种移植瘤生长,而circKDM1A过表达则产生相反的效果。双荧光素酶报告基因检测显示,circKDM1A直接与miR-889-3p结合,作为其分子海绵下调CPEB3。反过来,CPEB3与p53 mRNA 3'UTR中的CPE信号结合以稳定其表达。因此,circKDM1A介导的CPEB3下调抑制了p53 mRNA的稳定性并促进了BCa的恶性进展。总之,circKDM1A通过miR-889-3p/CPEB3/p53轴在BCa恶性增殖中发挥肿瘤抑制作用。CircKDM1A可能是BCa潜在的预后生物标志物和治疗靶点。