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Exploring the Arginine Methylome by Nuclear Magnetic Resonance Spectroscopy
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Exploring the Arginine Methylome by Nuclear Magnetic Resonance Spectroscopy

Published on: December 16, 2021

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ROS inhibits RORα degradation by decreasing its arginine methylation in liver cancer

Hyuntae Im1, Hee-Ji Baek2,3, Eunbi Yang2,3

  • 1Department of Molecular Bioscience, College of Biomedical Sciences, Kangwon National University, Chuncheon, Korea.

Cancer Science
|September 17, 2022
PubMed

Insights

Protein arginine methyltransferase 5 (PRMT5) targets the tumor suppressor RORα for degradation in liver cancer. Reactive oxygen species (ROS) reduce PRMT5, increasing RORα and inhibiting cancer progression.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Biochemistry

Background:

  • Retinoic acid receptor-related orphan receptor α (RORα) is a tumor suppressor regulating gene expression.
  • RORα degradation via lysine methylation is known, but other post-translational modifications (PTMs) are less understood, particularly in liver cancer.
  • Arginine methylation is a PTM affecting protein function, with histone H3 arginine methylation as a precedent.

Purpose of the Study:

  • To investigate the role of arginine methylation in RORα regulation.
  • To identify the enzyme responsible for RORα arginine methylation and its downstream effects.
  • To explore the impact of reactive oxygen species (ROS) on this pathway in liver cancer cells.

Main Methods:

  • Investigated RORα arginine methylation at R37 using protein arginine methyltransferase 5 (PRMT5).
  • Assessed the interaction between PRMT5, RORα, and the E3 ubiquitin ligase ITCH.
  • Analyzed the effect of hydrogen peroxide (H₂O₂)-induced ROS on PRMT5 and RORα levels in HepG2 cells.
  • Evaluated the impact of this pathway on liver cancer progression and apoptosis.

Main Results:

  • PRMT5 mediates RORα degradation through arginine methylation at R37.
  • PRMT5 regulates the interaction between ITCH and RORα via RORα arginine methylation, leading to ubiquitination and degradation.
  • ROS decrease PRMT5 levels, increasing RORα protein and inhibiting liver cancer progression by inducing apoptosis through the PRMT5-RORα-ITCH axis.

Conclusions:

  • PRMT5-mediated arginine methylation drives RORα degradation, impacting gene activation.
  • ROS signaling modulates liver cancer progression by influencing PRMT5 and RORα levels.
  • PRMT5 is a potential therapeutic target, and the ROS-PRMT5-RORα-ITCH axis offers new avenues for liver cancer treatment.
Keywords:
RORα-PRMT5-ITCHROSarginine methylationliver cancermethyl-degron

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