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Updated: Oct 4, 2025

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
07:50

Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer

Published on: September 18, 2020

5.7K

Demethylase ALKBH5 suppresses invasion of gastric cancer via PKMYT1 m6A modification

Yiyang Hu1, Chunli Gong1, Zhibin Li1

  • 1Department of Gastroenterology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.

Molecular Cancer
|February 4, 2022
PubMed
Abstract

Insights

This study reveals that decreased ALKBH5 expression promotes gastric cancer (GC) metastasis by upregulating PKMYT1. This ALKBH5-PKMYT1-IGF2BP3 pathway offers a new therapeutic target for treating GC metastasis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Gastric cancer (GC) poses a significant global health burden.
  • Metastasis is a primary reason for GC treatment failure.
  • The role of N6-methyladenosine (m6A) modification in GC metastasis remains underexplored.

Purpose of the Study:

  • To investigate the correlation between m6A modification and GC metastasis.
  • To identify key molecular players involved in GC metastasis.
  • To explore potential therapeutic targets for GC metastasis.

Main Methods:

  • Methylated RNA immunoprecipitation sequencing (MeRIP-seq) on GC tissues.
  • Quantitative real-time PCR (qRT-PCR), western blotting, and immunohistochemistry (IHC) for ALKBH5 expression analysis.
  • RNA sequencing, RNA pulldown, mass spectrometry, and RNA immunoprecipitation (RIP) to elucidate molecular mechanisms.
  • In vivo validation using a lung metastasis model via tail vein injection.

Main Results:

  • Reduced ALKBH5 expression in GC samples correlated with advanced metastasis.
  • ALKBH5 depletion enhanced GC cell metastasis, dependent on its demethylase activity.
  • PKMYT1 was identified as a downstream target of ALKBH5, promoting GC invasion and migration.
  • ALKBH5 regulates PKMYT1 expression in an m6A-dependent manner; IGF2BP3 stabilizes PKMYT1 mRNA via m6A modification.

Conclusions:

  • An ALKBH5-PKMYT1-IGF2BP3 regulatory axis in GC metastasis was established.
  • This pathway represents a novel therapeutic target for combating GC metastasis.
Keywords:
ALKBH5Demethylase activityGastric cancerInvasionMetastasisPKMYT1

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