Related Experiment Video

Updated: Jul 12, 2025

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
06:07

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

Published on: August 5, 2022

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DNMT1 determines osteosarcoma cell resistance to apoptosis by associatively modulating DNA and mRNA cytosine-5

Dongxing Shao1,2, Cihang Liu1,2, Yingying Wang2

  • 1Department of Biochemistry and Molecular Biology, Beijing Key Laboratory of Protein Posttranslational Modifications and Cell Function, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|October 31, 2023
PubMed

Insights

Chemotherapy induces DNA methylation (DNMT1) and suppresses RNA methylation (NSun2) to control osteosarcoma cell apoptosis. This DNA-RNA methylation crosstalk regulates anti-apoptotic genes, impacting cancer treatment.

Area of Science:

  • Epigenetics
  • Molecular Biology
  • Cancer Research

Background:

  • Cellular apoptosis is crucial for chemotherapy's anti-cancer effects.
  • DNA and messenger RNA (mRNA) 5-methylcytosine (m5C) modifications regulate apoptosis independently.
  • The interplay between DNA and mRNA methylation in apoptosis remains unexplored.

Purpose of the Study:

  • To investigate the crosstalk between DNA and mRNA methylation in osteosarcoma cell apoptosis.
  • To elucidate the roles of DNMT1 and NSun2 in regulating apoptosis during chemotherapy.

Main Methods:

  • Investigated the expression of DNMT1 and NSun2 during chemotherapy-induced osteosarcoma cell apoptosis.
  • Analyzed the methylation of the NSun2 promoter by DNMT1.
  • Examined the regulation of anti-apoptotic genes (AXL, NOTCH2, YAP1) by DNA and mRNA methylation.

Main Results:

  • DNMT1 expression increased, while NSun2 expression decreased during osteosarcoma cell apoptosis induced by chemotherapeutic drugs.
  • DNMT1 repressed NSun2 expression via promoter methylation.
  • DNMT1 and NSun2 collectively regulated anti-apoptotic genes AXL, NOTCH2, and YAP1 through DNA and mRNA methylation, respectively.
  • Chemotherapy exposure led to DNMT1 elevation, reducing anti-apoptotic gene expression via promoter methylation and NSun2 suppression, promoting apoptosis.

Conclusions:

  • A significant crosstalk exists between DNA and RNA cytosine methylations in determining osteosarcoma cell apoptosis resistance during chemotherapy.
  • This interplay provides new insights into osteosarcoma treatment strategies.
  • The findings add layers to the epigenetic control of gene expression.
Keywords:
5-MethylcytosineDNMT1NSun2apoptosisosteosarcoma

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