Related Experiment Video

Updated: Jan 14, 2026

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
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Published on: August 5, 2022

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RNA m1A methyltransferase TRMT61A promotes colorectal tumorigenesis by enhancing ONECUT2 mRNA stability and is a

Xiaoting Zhang1,2, Na Qin1,2, Fenfen Ji2

  • 1Department of Anaesthesia and Intensive Care and Peter Hung Pain Research Institute, The Chinese University of Hong Kong, Hong Kong, P. R. China.

Cancer Communications (London, England)
|October 17, 2025
PubMed
Abstract

Insights

RNA methyltransferase TRMT61A promotes colorectal cancer (CRC) by stabilizing key mRNAs. Inhibiting TRMT61A with novel therapies offers a promising strategy for CRC treatment.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • The role of N1-methyladenosine (m1A) in cancer remains largely unexplored.
  • RNA methyltransferase TRNA methyltransferase 61A (TRMT61A) is investigated for its function in colorectal cancer (CRC).

Purpose of the Study:

  • To explore the function of TRMT61A in CRC.
  • To evaluate TRMT61A as a potential therapeutic target for CRC.

Main Methods:

  • Assessed RNA m1A levels using liquid chromatography-mass spectrometry.
  • Investigated TRMT61A expression and clinical significance in five human CRC cohorts.
  • Elucidated TRMT61A function using cell lines, organoids, xenografts, and mouse models.
  • Performed integrated m1A-seq and RNA-seq analyses.
  • Developed nanoparticle-based siRNA and small molecule inhibitor targeting TRMT61A.

Main Results:

  • TRMT61A expression and total RNA m1A levels are elevated in primary CRCs, correlating with poor prognosis.
  • TRMT61A is essential for CRC tumorigenesis and progression, enhancing mRNA stability of targets like ONECUT2 in an m1A-dependent manner.
  • TRMT61A upregulates ONECUT2, which drives SOS1 transcription and activates the MAPK/ERK pathway in CRC.
  • Inhibition of TRMT61A demonstrated significant anti-CRC effects and safety in preclinical models.

Conclusions:

  • TRMT61A promotes CRC through the m1A-ONECUT2-SOS1-MAPK/ERK pathway.
  • Targeting TRMT61A presents a promising therapeutic strategy for colorectal cancer.
Keywords:
Colorectal CancerMAPK/ERKN1‐MethyladenosineTRMT61ATherapeutic target

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