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Downregulated RBM5 Enhances CARM1 Expression and Activates the PRKACA/GSK3β Signaling Pathway through Alternative

Yanping Zhang1, Fang Li2, Zhenwei Han1

  • 1Department of Urology, The Second Hospital of Hebei Medical University, Shijiazhuang 050011, China.

Cancers
|January 11, 2024
PubMed

Insights

Downregulated RNA-binding motif protein 5 (RBM5) accelerates bladder cancer by increasing coactivator-associated arginine methyltransferase 1 (CARM1) expression. This study reveals RBM5

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • RNA-binding motif protein 5 (RBM5) downregulation is linked to tumor progression, including bladder cancer (BC).
  • Alternative splicing (AS) and nonsense-mediated mRNA decay (NMD) are implicated in cancer progression.
  • The specific role of RBM5 in BC via AS-NMD pathways is not well understood.

Purpose of the Study:

  • To investigate the role of RBM5 in bladder cancer progression.
  • To elucidate the mechanism by which RBM5 influences bladder cancer through alternative splicing and NMD.
  • To identify potential therapeutic targets for bladder cancer.

Main Methods:

  • Analyzing RBM5 expression in BC cells and tissues.
  • Investigating the interaction between RBM5 and CARM1 mRNA.
  • Assessing the impact of RBM5 on the Wnt/β-catenin pathway.
  • Examining the role of PRKACA in BC progression.

Main Results:

  • RBM5 downregulation increased coactivator-associated arginine methyltransferase 1 (CARM1) expression in BC.
  • CARM1 activation of the Wnt/β-catenin axis promoted BC cell proliferation and poor prognosis.
  • RBM5 directly binds CARM1 mRNA, mediating AS-NMD to reduce CARM1 levels.
  • PRKACA, regulated by CARM1, promotes BC growth.

Conclusions:

  • A novel RBM5/CARM1/PRKACA regulatory axis controlling Wnt/β-catenin activation in BC was identified.
  • RBM5 functions to suppress BC progression by downregulating CARM1 via AS-NMD.
  • This axis represents a potential therapeutic target for bladder cancer treatment.
Keywords:
CARM1RBM5alternative splicingbladder cancernonsense-mediated mRNA decay

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