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Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
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The m6A methyltransferase METTL3 affects ferroptosis in non-small cell lung cancer by regulating the PTEN/PI3K/AKT

Bin Wu1, Danhong Li2, Yu Wang3

  • 1Department of Respiratoty, Affiliated Xiaoshan Hospital, Hangzhou Normal Uiniversity, No. 728, Yucai North Road, Xiaoshan District, Hangzhou, 311200, Zhejiang, China. tcmstudent@163.com.

Discover Oncology
|April 18, 2025
PubMed
Abstract

Insights

METTL3 promotes non-small cell lung cancer (NSCLC) by inhibiting ferroptosis via the PTEN/PI3K/AKT pathway. Targeting this pathway offers a potential therapeutic strategy for NSCLC treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Non-small cell lung cancer (NSCLC) is a significant global health concern.
  • METTL3 is implicated in promoting tumor development by suppressing ferroptosis.
  • Understanding METTL3's mechanism in NSCLC is crucial for developing new therapies.

Purpose of the Study:

  • To investigate the role and mechanism of METTL3 in non-small cell lung cancer (NSCLC).
  • To explore the relationship between METTL3, ferroptosis, and the PTEN/PI3K/AKT pathway in NSCLC.

Main Methods:

  • Analysis of METTL3 and PTEN expression in NSCLC using the UALCAN database.
  • In vitro experiments involving cell transfection (sh-METTL3, oe-METTL3, sh-PTEN) in NSCLC cell lines.
  • Assessment of cell proliferation, migration, invasion, apoptosis, m6A methylation, oxidative stress, and Fe2+ content.
  • Quantification of GPX4, PTEN, PI3K, and AKT phosphorylation levels.

Main Results:

  • METTL3 expression is upregulated in NSCLC and correlates with tumor stage.
  • METTL3 overexpression enhances NSCLC cell malignancy, increases m6A methylation, reduces oxidative stress, and inhibits ferroptosis and apoptosis.
  • METTL3 knockdown reverses these effects, and PTEN knockdown rescues METTL3 knockdown-induced ferroptosis.

Conclusions:

  • METTL3 inhibits ferroptosis in NSCLC by activating the PTEN/PI3K/AKT pathway.
  • The METTL3-mediated PTEN/PI3K/AKT pathway represents a potential therapeutic target for NSCLC.
Keywords:
FerroptosisGPX4METTL3Non-small cell lung cancerPTEN/PI3K/AKT

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