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Updated: May 21, 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

Published on: August 7, 2021

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PRMT5 attenuates regorafenib-induced DNA damage in hepatocellular carcinoma cells through symmetric dimethylation of

Wendi Bi1,2, Xiaojuan Sun1, Qiuyun Yi1,3

  • 1Department of Laboratory Diagnosis, Third Affiliated Hospital of Naval Medical University (Second Military Medical University), Shanghai, China.

Journal of Gastrointestinal Oncology
|March 21, 2025
PubMed
Abstract

Insights

Protein arginine methyltransferase 5 (PRMT5) promotes DNA repair and regorafenib resistance in hepatocellular carcinoma (HCC) by methylating RPL14. Targeting RPL14 can enhance HCC cell sensitivity to regorafenib, overcoming drug resistance.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Hepatocellular carcinoma (HCC) treatment faces challenges with resistance to targeted therapies like regorafenib.
  • Enhancing HCC cell sensitivity to regorafenib is critical for improving patient outcomes.
  • Understanding resistance mechanisms is key to developing effective therapeutic strategies.

Purpose of the Study:

  • To investigate the role of PRMT5 in HCC and its effect on regorafenib sensitivity.
  • To elucidate the regulatory relationship between PRMT5 and RPL14.
  • To determine the impact of PRMT5 and RPL14 on DNA damage repair and drug resistance in HCC.

Main Methods:

  • Constructed a PRMT5-overexpressing HCC cell line using lentiviral infection.
  • Utilized immunoprecipitation and mass spectrometry to confirm PRMT5-RPL14 interaction and PRMT5's catalytic activity.
  • Assessed DNA damage (γ-H2AX) and repair (RAD51) markers via Western blot and immunofluorescence following RPL14 knockdown and regorafenib treatment.

Main Results:

  • Confirmed PRMT5 catalyzes the symmetric dimethylation of RPL14, stabilizing the protein.
  • RPL14 knockdown inhibited HCC cell proliferation and increased sensitivity to regorafenib by disrupting DNA damage repair.
  • PRMT5 overexpression reduced DNA damage markers and enhanced survival, while RPL14 knockdown increased damage markers and decreased survival, with combined effects showing significant DNA damage.

Conclusions:

  • PRMT5-mediated RPL14 methylation promotes DNA damage repair, contributing to regorafenib resistance in HCC.
  • RPL14 is crucial for PRMT5-driven enhancement of DNA damage repair and reduced drug sensitivity.
  • RPL14 represents a potential therapeutic target to overcome regorafenib resistance in HCC.
Keywords:
DNA damage repairHepatocellular carcinoma (HCC)PRMT5RPL14regorafenib

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