METTL14 plays an oncogenic role in NSCLC by modulating ferroptosis and the m6A modification of GPX4

Abstract

Context

N6-methyladenosine (m6A) of RNA is involved in the progression of non-small cell lung cancer (NSCLC).

Objective

This study investigated the role of METTL14 in NSCLC and the mechanism.

Materials and methods

Expression levels were assessed by quantitative real-time PCR and ELISA assays. Cells viability was assessed by cell counting kit-8. M6A methylation was analysed by methylated RNA immunoprecipitation (MeRIP), RIP, luciferase assay, and mRNA stability assay.

Results

The results showed that METTL14 was highly expressed in NSCLC tissues and cell lines. Knockdown of METTL14 inhibited the cell viability while induced ferroptosis of NSCLC cells. Mechanistically, METTL14 interacts with GPX4, mediates m6A modification of GPX4, enhances its mRNA stability, and upregulates its expression. In addition, IGF2BP1 recognises the m6A-methylated GPX4 and mediates the elevated mRNA stability. Moreover, GPX4 reversed the effects of METTL14 depletion.

Discussion and conclusion

The METTL14/GPX4 axis promotes NSCLC progression by inhibiting cell ferroptosis through the recognition of m6A modification mediated by IGF2BP1.

Keywords:

• METTL14
• lung cancer
• ferroptosis
• m6A
• GPX4

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent to publish

Not applicable.

Author contributions

All authors participated in the design, interpretation of the studies and analysis of the data and review of the manuscript. Y L drafted the work and revised it critically for important intellectual content; K H and B X were responsible for the acquisition, analysis, or interpretation of data for the work; X C made substantial contributions to the conception or design of the work. All authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Additional information

Funding

The work was supported by Public Welfare Project of Jinhua Science and Technology Program Project (Clinical application study of predicting long-term air leakage after thoracoscopic lobectomy based on HRCT emphysema grade and Cardiopulmonary exercise test) under grant No.2022–4-120; Jinhua Municipal Central Hospital Young and Middle-aged Scientific Research Start-up Fund under grant No. JH2023-2–04.