Related Experiment Video

Updated: Jul 12, 2026

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

TRDMT1-mediated mRNA m5C methylation decreases chemotherapy sensitivity by activating homologous

Wenhao Luo1, Hao Chen1, Yifan Fu1

  • 1Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.

Cancer Letters
|July 10, 2026
PubMed

Insights

TRDMT1 regulates mRNA methylation in pancreatic cancer, impacting chemotherapy response. Targeting TRDMT1 may overcome chemoresistance by affecting DNA repair and the IRS2/PI3K/AKT pathway.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with chemotherapy as a primary treatment.
  • Identifying novel regulators of chemoresistance is crucial for improving PDAC patient outcomes.

Purpose of the Study:

  • To investigate the role of TRDMT1 in PDAC chemoresistance.
  • To elucidate the mechanism by which TRDMT1 influences mRNA methylation and therapeutic response.

Main Methods:

  • Transcriptomic analysis of gemcitabine-treated PDAC cells.
  • TRDMT1 deficiency assessment in PDAC cells and mouse models.
  • mRNA m5C modification sequencing.
  • Analysis of homologous recombination protein recruitment.
  • Investigation of the IRS2/PI3K/AKT signaling pathway.

Main Results:

  • TRDMT1 was identified as a key regulator of mRNA m5C methylation in PDAC.
  • TRDMT1 deficiency reduced PDAC cell malignancy and enhanced sensitivity to multiple chemotherapies.
  • TRDMT1 deletion impaired homologous recombination repair protein recruitment.
  • IRS2 showed decreased m5C methylation and expression in TRDMT1-deficient cells, implicating the IRS2/PI3K/AKT pathway.
  • TRDMT1 promotes chemoresistance in PDAC patient data and mouse models.

Conclusions:

  • TRDMT1-mediated mRNA m5C methylation is vital for homologous recombination repair in PDAC.
  • TRDMT1 is a potential therapeutic target to overcome chemoresistance in pancreatic cancer.
Keywords:
ChemotherapyIRS2Pancreatic ductal adenocarcinomaTRDMT1mRNA m5C methylation

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