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

doi:10.1016/j.isci.2024.109624

circKDM1A suppresses bladder cancer progression by sponging miR-889-3p/CPEB3 and stabilizing p53 mRNA

iScience. 2024 Mar 29;27(4):109624. doi: 10.1016/j.isci.2024.109624. eCollection 2024 Apr 19.

Authors

Haotian Chen^{1

2}, Jing Wen³, Wentao Zhang^{1

2}, Wenchao Ma⁴, Yadong Guo^{1

2}, Liliang Shen⁵, Zhijin Zhang^{1

2}, Fuhan Yang^{1

2}, Yue Zhang⁶, Yaohui Gao⁷, Tianyuan Xu^{1

2}, Yang Yan^{1

2}, Wei Li^{1

2}, Junfeng Zhang^{1

2}, Shiyu Mao^{1

2}, Xudong Yao^{1

2}

Affiliations

¹ Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
² Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, China.
³ Institute of Energy Metabolism and Health, Shanghai Tenth People's Hospital, Tongji University School of Medicine Shanghai, Shanghai 200072, P.R. China.
⁴ 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.
⁵ Department of Urology, The Affiliated People's Hospital of Ningbo University, Ningbo, China.
⁶ Department of Central Laboratory, Clinical Medicine Scientific and Technical Innovation Park, Shanghai Tenth People's Hospital, Shanghai 200435, China.
⁷ Department of Pathology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.

Abstract

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.

Keywords: Bioinformatics; Cancer; Cell biology; Molecular biology.