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YTHDF2 Inhibits Gastric Cancer Cell Growth by Regulating FOXC2 Signaling Pathway

Xudong Shen1, Kui Zhao2, Liming Xu3

  • 1Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Frontiers in Genetics
|January 28, 2021
PubMed
Abstract

Insights

YTH domain family 2 (YTHDF2) inhibits gastric cancer growth by downregulating FOXC2. Lower YTHDF2 expression correlates with advanced gastric cancer stages and poorer patient survival, suggesting YTHDF2 as a potential prognostic marker.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Regulation

Background:

  • Gastric cancer (GC) is a prevalent global malignancy.
  • YTH domain family 2 (YTHDF2) regulates mRNA stability and localization via m6A binding.
  • YTHDF2's role and mechanism in gastric cancer progression were previously undocumented.

Purpose of the Study:

  • To investigate the expression and function of YTHDF2 in gastric cancer.
  • To elucidate the molecular mechanism underlying YTHDF2's effect on GC growth.
  • To evaluate YTHDF2 as a potential prognostic biomarker for gastric cancer.

Main Methods:

  • Analysis of YTHDF2 expression in public databases and patient samples.
  • In vitro and in vivo assays to assess YTHDF2's impact on GC cell growth.
  • RNA sequencing to identify YTHDF2-regulated signaling pathways, with experimental validation.
  • FOXC2 knockout experiments to confirm pathway involvement.

Main Results:

  • YTHDF2 exhibited lower expression in GC tissues and cells, inhibiting GC cell proliferation.
  • YTHDF2 expression levels correlated significantly with GC stage and patient survival.
  • Overexpression of YTHDF2 led to reduced protein expression in the Forkhead box protein C2 (FOXC2) signaling pathway.
  • FOXC2 knockout abrogated the inhibitory effect of YTHDF2 on GC cells.

Conclusions:

  • YTHDF2 suppresses gastric cancer cell growth through negative regulation of the FOXC2 pathway.
  • YTHDF2 demonstrates potential as a prognostic marker for gastric cancer patients.
Keywords:
FOXC2M6AYTHDF2cell growthgastric cancer

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