The Effect of M6a Methyltransferase Mettl3 Mediated Tmem30a Regulation on Tumor Energy Metabolism and Cisplatin Anti-Tumor Activity in Oral Squamous Cell Carcinoma

Abstract

A bstractAims: Cisplatin is still one of the most commonly used first-line treatments for advanced and recurrent oral squamous cell carcinoma patients in clinical practice. However, the decrease in tumor sensitivity to cisplatin weakens its therapeutic effect. There is still limited research on the effect of METTL3-mediated methylation of m6A on cisplatin sensitivity in oral squamous cell carcinoma. TMEM30A widely exists in biomembranes and regulates the lipid asymmetry of the membrane, but there is no report on its function in oral squamous cell carcinoma. This study aims to explore the specific mechanism by which METTL3 regulates m6A methylation of TMEM30A and affects the occurrence and development of oral squamous cell carcinoma, and further investigate the effects of METTL3 and TMEM30A on the anti-tumor activity of cisplatin.Key findings: In oral squamous cell carcinoma, METTL3 plays a pro cancer role and weakens the anti-tumor efficacy of cisplatin; METTL3 binds to TMEM30A through m6A methylation modification, affecting the expression of TMEM30A; The abnormally high expression of TMEM30A in tumors not only weakens cisplatin sensitivity, but also enhances the malignant evolution of cancer cells, regulates the metabolic balance of ATP and lactate in cells, and is a potential oncogenic gene.Significance : TMEM30A promotes malignant progression of tumors through METTL3 mediated m6A methylation modification, participates in maintaining the balance of tumor ATP and lactate metabolism, and thus reduces the anti-tumor activity of cisplatin. TMEM30A is a potential gene target for cisplatin anti-tumor activity in oral squamous cell carcinoma.

Note:
Funding declaration: This study was supported by the National Natural Science Foundation of China (No. 81960492), the Science and Technology Plan Project of Jiangxi Provincial Health Commission (No. 202410281), and the Science and Technology Plan Project of Jiangxi Provincial Health Commission (No. 202210680).

Conflict of Interests: All authors declare that they have no conflict of interest.

Ethical Approval: Animal experiments and ethical compliance with relevant guidelines(Ethics Approval Number: SYXK (gan) 2023-0002).

Keywords: Oral squamous carcinoma, m6A methylation, METTL3, TMEM30A, Cisplatin antitumor activity