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

Haotian Chen1,2, Jing Wen3, Wentao Zhang1,2

  • 1Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.

Iscience
|April 18, 2024
PubMed

Insights

Circular RNAs (circRNAs) act as tumor suppressors in bladder cancer (BCa). CircKDM1A inhibits BCa proliferation by regulating the miR-889-3p/CPEB3/p53 pathway, offering potential therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Circular RNAs (circRNAs) are implicated in various cancers, but their specific roles in bladder cancer (BCa) proliferation remain unclear.
  • Understanding the molecular mechanisms of circRNAs in BCa is essential for developing novel therapeutic strategies.

Purpose of the Study:

  • To investigate the function and molecular mechanism of circKDM1A in the malignant proliferation of bladder cancer.
  • To explore the potential of circKDM1A as a biomarker and therapeutic target for BCa.

Main Methods:

  • Quantitative real-time PCR to assess circKDM1A expression in BCa tissues and cells.
  • Cell proliferation assays and xenograft models to evaluate the functional role of circKDM1A.
  • Dual-luciferase reporter assays to confirm the interaction between circKDM1A, miR-889-3p, and CPEB3.
  • Western blotting to analyze protein expression levels of CPEB3 and p53.

Main Results:

  • CircKDM1A was found to be significantly downregulated in BCa tissues and cells.
  • Knockdown of circKDM1A promoted BCa cell proliferation and tumor growth, while overexpression had the opposite effect.
  • CircKDM1A acted as a molecular sponge for miR-889-3p, inhibiting CPEB3 expression.
  • CPEB3 regulated p53 mRNA stability via the CPE signal in its 3'UTR, and circKDM1A-mediated CPEB3 downregulation reduced p53 stability, promoting BCa progression.

Conclusions:

  • CircKDM1A functions as a tumor suppressor in bladder cancer by regulating the miR-889-3p/CPEB3/p53 signaling axis.
  • CircKDM1A may serve as a potential prognostic biomarker and therapeutic target for bladder cancer.
Keywords:
BioinformaticsCancerCell biologyMolecular biology

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