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

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 a...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2024-04-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004224008460
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author 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
author_facet 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
author_sort Haotian Chen
collection DOAJ
description 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.
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spelling doaj.art-2e2305bdce3b4f42b265dd035de0de412024-04-11T04:41:49ZengElsevieriScience2589-00422024-04-01274109624circKDM1A suppresses bladder cancer progression by sponging miR-889-3p/CPEB3 and stabilizing p53 mRNAHaotian Chen0Jing Wen1Wentao Zhang2Wenchao Ma3Yadong Guo4Liliang Shen5Zhijin Zhang6Fuhan Yang7Yue Zhang8Yaohui Gao9Tianyuan Xu10Yang Yan11Wei Li12Junfeng Zhang13Shiyu Mao14Xudong Yao15Department of Urology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, China; Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, ChinaInstitute of Energy Metabolism and Health, Shanghai Tenth People’s Hospital, Tongji University School of Medicine Shanghai, Shanghai 200072, P.R. ChinaDepartment of Urology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, China; Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Reproduction, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, ChinaDepartment of Urology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, China; Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Urology, The Affiliated People’s Hospital of Ningbo University, Ningbo, ChinaDepartment of Urology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, China; Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Urology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, China; Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Central Laboratory, Clinical Medicine Scientific and Technical Innovation Park, Shanghai Tenth People’s Hospital, Shanghai 200435, ChinaDepartment of Pathology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Urology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, China; Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Urology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, China; Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, ChinaDepartment of Urology, Shanghai Tenth People’s Hospital, School of Medicine, Tongji University, Shanghai, China; Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, ChinaDepartment 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 authorDepartment 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 authorDepartment 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 authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004224008460Molecular biologyCell biologyBioinformaticsCancer
spellingShingle 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
circKDM1A suppresses bladder cancer progression by sponging miR-889-3p/CPEB3 and stabilizing p53 mRNA
iScience
Molecular biology
Cell biology
Bioinformatics
Cancer
title circKDM1A suppresses bladder cancer progression by sponging miR-889-3p/CPEB3 and stabilizing p53 mRNA
title_full circKDM1A suppresses bladder cancer progression by sponging miR-889-3p/CPEB3 and stabilizing p53 mRNA
title_fullStr circKDM1A suppresses bladder cancer progression by sponging miR-889-3p/CPEB3 and stabilizing p53 mRNA
title_full_unstemmed circKDM1A suppresses bladder cancer progression by sponging miR-889-3p/CPEB3 and stabilizing p53 mRNA
title_short circKDM1A suppresses bladder cancer progression by sponging miR-889-3p/CPEB3 and stabilizing p53 mRNA
title_sort circkdm1a suppresses bladder cancer progression by sponging mir 889 3p cpeb3 and stabilizing p53 mrna
topic Molecular biology
Cell biology
Bioinformatics
Cancer
url http://www.sciencedirect.com/science/article/pii/S2589004224008460
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