METTL14 drives growth and metastasis of non-small cell lung cancer by regulating pri-miR-93-5p maturation and TXNIP expression

Background: Non-small cell lung cancer (NSCLC) is a prevalent and aggressive malignancy responsible for a significant number of cancer-related deaths worldwide. Unraveling the molecular mechanisms governing NSCLC growth and metastasis is crucial for the identification of novel therapeutic targets and the development of effective anti-cancer strategies. One such mechanism of interest is the involvement of METTL14, an RNA methyltransferase implicated in various cellular processes, in NSCLC progression.

Objective: The objective of this study was to investigate the role of METTL14 in NSCLC development and metastasis and to elucidate the underlying molecular mechanisms. By understanding the impact of METTL14 on NSCLC pathogenesis, the study aimed to identify potential avenues for targeted therapies in NSCLC treatment.

Methods: We used bioinformatics and high-throughput transcriptome sequencing analyses to screen regulatory mechanisms affecting NSCLC. The Kaplan-Meier method assessed the correlation between METTL14 expression and the prognosis of NSCLC patients. The effects of manipulated METTL14 on malignant phenotypes of NSCLC cells were examined by colony formation assay, flow cytometry, scratch assay, and Transwell assay. The tumorigenic capacity and metastatic potential of NSCLC cells in vivo were evaluated in nude mice.

Results: METTL14 was overexpressed in NSCLC tissues and cell lines. Its high expression indicated a poor prognosis for NSCLC patients. METTL14 silencing promoted apoptosis and repressed proliferation, migration, and invasion of NSCLC cells. miR-93-5p targeted and inhibited TXNIP. METTL14 increased miR-93-5p expression and matured pri-miR-93-5p through m6A alteration to inhibit TXNIP, thereby inhibiting NSCLC cell apoptosis. By controlling the miR-93-5p/TXNIP axis, METTL14 increased the tumorigenic potential and lung metastasis of NSCLC cells in nude mice.

Conclusion: This study revealed a role for METTL14 in the contribution to NSCLC development and metastasis and identified METTL14 as a potential target for NSCLC treatment.