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Updated: Jul 12, 2025

Quantitative Methods to Study Protein Arginine Methyltransferase 1-9 Activity in Cells
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Quantitative Methods to Study Protein Arginine Methyltransferase 1-9 Activity in Cells

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Antitumor Effects of PRMT5 Inhibition in Sarcomas

Stéphanie Verbeke1,2, Aurélien Bourdon1,2, Jean-Philippe Guegan3

  • 1Sarcoma Unit, Bergonié Institute, Bordeaux, France.

Cancer Research Communications
|October 20, 2023
PubMed

Insights

Targeting Protein Arginine Methyltransferase 5 (PRMT5) shows therapeutic potential for soft-tissue sarcomas (STS). PRMT5 inhibition reduced tumor growth and regulated cancer cell metabolism, suggesting it as a viable treatment target for STS patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Soft-tissue sarcomas (STS) present limited therapeutic avenues for patients.
  • Protein arginine methyltransferase 5 (PRMT5) is an established anticancer target, primarily studied in epithelial tumors.
  • The role and therapeutic potential of PRMT5 inhibition in STS remain largely unexplored.

Purpose of the Study:

  • To evaluate the prognostic significance of PRMT5 expression in STS patient cohorts.
  • To investigate the antitumor effects of PRMT5 inhibition using the selective compound GSK3326595 (GSK595) in vitro and in vivo.
  • To elucidate the underlying mechanisms of PRMT5 inhibition on STS cell metabolism.

Main Methods:

  • Prognostic value assessment of PRMT5 expression in two STS patient cohorts.
  • In vitro assays (MTT, apoptosis, cell cycle, clonogenicity, proliferation) using GSK595 on STS cell lines.
  • In vivo studies in two animal models to assess GSK595's effect on tumor growth.
  • Mechanism of action studies including RNA sequencing, metabolic pathway analysis, Western blotting, and glucose uptake/lactate production assays.

Main Results:

  • High PRMT5 gene expression correlated with poorer metastasis-free survival in STS patients.
  • GSK595 treatment reduced proliferation, clonogenicity, and in vivo tumor growth of STS.
  • PRMT5 inhibition led to the downregulation of aerobic glycolysis, including glucose uptake and lactate production.

Conclusions:

  • PRMT5 plays a crucial role in regulating STS cell metabolism.
  • PRMT5 inhibition demonstrates significant antitumor activity in STS models.
  • PRMT5 represents a promising therapeutic target for soft-tissue sarcomas, warranting further clinical investigation.

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