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PRMT1 promotes pancreatic cancer development and resistance to chemotherapy

Bomin Ku1, David Eisenbarth2, Seonguk Baek1

  • 1National Creative Research Center for Cell Plasticity, KAIST Stem Cell Center, Department of Biological Sciences, KAIST, Daejeon 34141, Republic of Korea.

Cell Reports. Medicine
|March 9, 2024
PubMed

Insights

This study identifies PRMT1 as a key driver in pancreatic cancer development. Inhibiting PRMT1 shows promise for new combination therapies against this lethal disease.

Area of Science:

  • Oncology
  • Epigenetics
  • Molecular Biology

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with limited treatment options.
  • The role of epigenetic regulation in PDAC development and as a therapeutic target is not well understood.

Purpose of the Study:

  • To investigate the role of PRMT1 in pancreatic cancer.
  • To evaluate PRMT1 as a potential therapeutic target for PDAC.

Main Methods:

  • Assessed PRMT1 expression in murine and human pancreatic cancer.
  • Utilized a KRAS-dependent mouse model to study PRMT1 deletion effects.
  • Performed multi-omics analyses to understand PRMT1's impact on chromatin and transcription.
  • Investigated the synergistic effect of PRMT1 inhibition with gemcitabine in vitro and in vivo.

Main Results:

  • PRMT1 is highly expressed in pancreatic cancer and is crucial for cancer cell proliferation and tumorigenesis.
  • PRMT1 deletion delays tumor development and reduces tumorigenic capacity by altering chromatin accessibility and transcription, leading to decreased glycolysis.
  • Pharmacological inhibition of PRMT1 combined with gemcitabine demonstrates synergistic effects on pancreatic tumor growth.

Conclusions:

  • PRMT1 is a critical regulator in the development of pancreatic cancer.
  • PRMT1 represents a promising therapeutic target for novel combination strategies in PDAC treatment.
Keywords:
PRMT1chemotherapy resistancechromatin accessibilitycombination therapydrug synergygemcitabineglycolysishistone methylationpancreatic cancerprotein arginine methyl transferase 1tumor metabolism

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