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M6A modification regulates tumor suppressor DIRAS1 expression in cervical cancer cells

Yu-Yan Wang1, Lian-Hua Ye2, An-Qi Zhao3

  • 1Department of Obstetrics and Gynecology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China.

Cancer Biology & Therapy
|February 19, 2024
PubMed

Insights

DIRAS1 acts as a tumor suppressor in cervical cancer, with its expression significantly reduced in tumors. Its regulation involves m6A modification, impacting cancer cell proliferation and metastasis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • DIRAS family GTPase 1 (DIRAS1) is a potential tumor suppressor.
  • Its role and expression in cervical cancer are not well understood.

Purpose of the Study:

  • To investigate the expression pattern and function of DIRAS1 in cervical cancer.
  • To explore the regulatory mechanisms of DIRAS1, including epigenetic modifications.

Main Methods:

  • DIRAS1 knockdown and overexpression in C33A and SiHa cells.
  • Analysis of DIRAS1 mRNA and protein levels in cervical cancer tissues.
  • Treatment with epigenetic inhibitors (5-Azacytidine, SAHA) and FTO inhibitor (FB23-2).
  • Investigation of m6A modification enzymes (METTL3, METTL14, FTO, ALKBH5).

Main Results:

  • DIRAS1 knockdown promoted cervical cancer cell proliferation, migration, and invasion.
  • DIRAS1 overexpression inhibited cell viability and motility.
  • DIRAS1 mRNA and protein levels were significantly lower in cervical cancer tissues.
  • DIRAS1 expression negatively correlated with pathological grade.
  • Epigenetic inhibitors affected DIRAS1 mRNA but not protein levels.
  • m6A modification enzymes differentially regulated DIRAS1 mRNA and protein levels.

Conclusions:

  • DIRAS1 exhibits significant anti-oncogenic activity in cervical cancer.
  • DIRAS1 expression is downregulated in cervical cancer, potentially due to m6A modification.
  • m6A modification plays a crucial role in regulating DIRAS1 mRNA stability and protein translation in cervical cancer.
Keywords:
Cervical cancerDIRAS1epigenetic regulationm6A

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