The effect of m6A methyltransferase METTL3 mediated TMEM30A regulation on tumor energy metabolism and cisplatin anti-tumor activity in oral squamous cell carcinoma

• Published in: Life sciences (1973) 2024-12, Vol.358, p.123122, Article 123122
• Main Authors: Yuan, Wei, Ouyang, Shaobo, Lv, Qiaoli, Liao, Lan
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - pharmacology; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell Line, Tumor; Cell Proliferation - drug effects; Cisplatin - pharmacology; Cisplatin anti-tumor activity; Energy Metabolism - drug effects; Gene Expression Regulation, Neoplastic - drug effects; Humans; m6A methylation; Male; Membrane Proteins - genetics; Membrane Proteins - metabolism; Methyltransferases - genetics; Methyltransferases - metabolism; METTL3; Mice; Mice, Inbred BALB C; Mice, Nude; Mouth Neoplasms - drug therapy; Mouth Neoplasms - genetics; Mouth Neoplasms - metabolism; Mouth Neoplasms - pathology; Oral squamous cell carcinoma; TMEM30A
• ISSN: 0024-3205; 1879-0631; 1879-0631
• DOI: 10.1016/j.lfs.2024.123122

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