METTL3 promotes Non-Small-Cell Lung Cancer Growth and Metastasis by Inhibiting FDX1 Through Copper Death-Associated Pri-miR-21-5p Maturation

Abstract

Objective:

We probed into the significance of METTL3 in the maturation process of pri-miR-21-5p. We specifically investigated its impact on the regulation of FDX1 and its involvement in the progression of non-small-cell lung cancer (NSCLC).

Methods:

The Cancer Genome Atlas (TCGA) identified NSCLC factors. Methylation-specific PCR (MSP), clonogenic tests and flow cytometry analyzed cells. Methylated RNA immunoprecipitation (Me-RIP) and dual-luciferase studied miR-21-5p/FDX1. Mice xenografts showed METTL3’s tumorigenic effect.

Results:

METTL3, with high expression but low methylation in NSCLC, influenced cell behaviors. Its suppression reduced oncogenic properties. METTL3 enhanced miR-21-5p maturation, targeting FDX1 and boosting NSCLC tumorigenicity in mice.

Conclusion:

METTL3 may promote NSCLC development by facilitating pri-miR-21-5p maturation, upregulating miR-21-5p and targeting inhibition of FDX1.

Plain language summary

We investigated a protein called METTL3, which is overly active in lung cancer cells, and how it affects the function of other small molecules. We discovered that as the activity of METTL3 increases, the growth and mobility of lung cancer cells also enhance, potentially accelerating the progression of lung cancer. Through a series of experiments, we observed how METTL3 interacts with other small molecules and further influences the behavior of lung cancer cells. This study helps us understand the role of METTL3 in the development of lung cancer and may offer new strategies for future treatments.

Tweetable abstract

METTL3 aids NSCLC progression by boosting miR-21-5p maturation, targeting FDX1. Understanding this can open new NSCLC treatment avenues.

Graphical abstract

Keywords::

• DNA methylation
• FDX1
• m6A methylation transferase
• m6A modification
• METTL3
• miR-21-5p
• NSCLC
• pri-miR-21-5p

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.tandfonline.com/doi/suppl/10.2217/epi-2023-0230

Author contributions

S Qian and J Liu wrote the paper and conceived and designed the experiments, W Liao analyzed the data, and F Wang collected and provided the sample for this study. All authors have read and approved the final submitted manuscript.

Financial disclosure

This study was supported by Quzhou Science and Technology Bureau 2023 Guiding Science and Technology Research Project (2023ZD031).

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval (Animal committee of The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital (QZRMYY-20231209-001).

Data sharing statement

The data that supports the findings of this study are available on request from the corresponding author.