FTO Inhibits Epithelial Ovarian Cancer Progression by Destabilising SNAI1 mRNA through IGF2BP2

Meige Sun1, Xiaocui Zhang1, Fangfang Bi1

  • 1Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China.

Cancers
|November 11, 2022
PubMed

Insights

Fat mass and obesity-associated protein (FTO) inhibits epithelial ovarian cancer (EOC) progression by reducing SNAI1 mRNA stability. This FTO-IGF2BP2-SNAI1 pathway offers a potential therapeutic target for EOC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Epigenetics

Background:

  • Fat mass and obesity-associated protein (FTO) plays a role in various diseases, including cancers.
  • The specific function of FTO in epithelial ovarian cancer (EOC) pathogenesis and its target genes are not fully understood.

Purpose of the Study:

  • To elucidate the functional role of FTO in EOC development.
  • To investigate the molecular mechanisms by which FTO influences EOC progression.
  • To identify potential therapeutic targets within the FTO regulatory network in EOC.

Main Methods:

  • In vitro and in vivo functional assays to assess FTO's biological functions.
  • m6A RNA immunoprecipitation (MeRIP) and RIP experiments to confirm m6A modification and binding sites.
  • Actinomycin D assay to determine RNA stability.

Main Results:

  • FTO expression was found to be downregulated in EOC, correlating with increased m6A levels and higher FIGO stages.
  • FTO reduced the m6A modification and stability of SNAI1 mRNA, leading to SNAI1 downregulation and inhibition of epithelial-mesenchymal transition (EMT).
  • IGF2BP2 was identified as an m6A reader that binds to SNAI1 mRNA, promoting its stability in an FTO-dependent manner.

Conclusions:

  • FTO inhibits EOC cell growth and metastasis by downregulating SNAI1 expression via an m6A-IGF2BP2-dependent mechanism.
  • The FTO-IGF2BP2-SNAI1 axis represents a promising therapeutic strategy for epithelial ovarian cancer.

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