circKDM1A suppresses bladder cancer progression by sponging miR-889-3p/CPEB3 and stabilizing p53 mRNA
Haotian Chen,
Jing Wen,
Wentao Zhang,
Wenchao Ma,
Yadong Guo,
Liliang Shen,
Zhijin Zhang,
Fuhan Yang,
Yue Zhang,
Yaohui Gao,
Tianyuan Xu,
Yang Yan,
Wei Li,
Junfeng Zhang,
Shiyu Mao,
Xudong Yao
Affiliations
Haotian Chen
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
Jing Wen
Institute of Energy Metabolism and Health, Shanghai Tenth People’s Hospital, Tongji University School of Medicine Shanghai, Shanghai 200072, P.R. China
Wentao Zhang
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
Wenchao Ma
Department of Reproduction, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, China
Yadong Guo
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
Liliang Shen
Department of Urology, The Affiliated People’s Hospital of Ningbo University, Ningbo, China
Zhijin Zhang
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
Fuhan Yang
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
Yue Zhang
Department of Central Laboratory, Clinical Medicine Scientific and Technical Innovation Park, Shanghai Tenth People’s Hospital, Shanghai 200435, China
Yaohui Gao
Department of Pathology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, China
Tianyuan Xu
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
Yang Yan
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
Wei Li
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
Junfeng Zhang
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; Corresponding author
Shiyu Mao
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; Corresponding author
Xudong Yao
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; Corresponding author
Summary: 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.
