Related Experiment Video

Updated: Jun 12, 2025

The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers
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The Use of Reverse Phase Protein Arrays RPPA to Explore Protein Expression Variation within Individual Renal Cell Cancers

Published on: January 22, 2013

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PRMT1 inhibition perturbs RNA metabolism and induces DNA damage in clear cell renal cell carcinoma

Joseph Walton1,2, Angel S N Ng1, Karen Arevalo1

  • 1Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.

Nature Communications
|September 19, 2024
PubMed

Insights

Clear cell renal cell carcinoma (ccRCC) may be treatable with epigenetic drugs. Targeting protein arginine methyltransferase 1 (PRMT1) with MS023 inhibits ccRCC growth by disrupting DNA repair and mRNA metabolism.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Clear cell renal cell carcinoma (ccRCC) frequently involves VHL gene loss and co-deletions in chromatin-regulating genes.
  • These genetic alterations suggest potential vulnerabilities to epigenetic therapies.

Purpose of the Study:

  • To screen epigenetic regulators for therapeutic targets in ccRCC.
  • To investigate the antitumorigenic effects and mechanism of action of identified compounds.

Main Methods:

  • Screening of a chemical probe library against ccRCC models.
  • Targeted knockdown of specific genes.
  • Cell cycle and DNA damage assays.
  • Proteomics and mRNA metabolism analysis.

Main Results:

  • MS023, a protein arginine methyltransferase (PRMT) inhibitor, demonstrated antitumorigenic activity in ccRCC models.
  • PRMT1 was identified as a critical dependency for ccRCC growth.
  • MS023 treatment and PRMT1 knockdown impaired cell cycle progression and DNA damage repair.
  • PRMT1 inhibition led to widespread disruptions in mRNA metabolism, R-loop accumulation, and DNA damage.

Conclusions:

  • PRMT1 is a critical driver of ccRCC and a potential therapeutic target.
  • Targeting PRMT1 with inhibitors like MS023 offers a mechanism-based strategy for ccRCC treatment.

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