{"title":"m6A甲基转移酶METTL3介导的TMEM30A调控对口腔鳞状细胞癌肿瘤能量代谢和顺铂抗肿瘤活性的影响","authors":"Wei Yuan, Shaobo Ouyang, Qiaoli Lv, Lan Liao","doi":"10.1016/j.lfs.2024.123122","DOIUrl":null,"url":null,"abstract":"<p><strong>Aims: </strong>Cisplatin (CDDP) 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 CDDP weakens its therapeutic effect. There is still limited research on the effect of METTL3-mediated methylation of m6A on CDDP sensitivity in oral squamous cell carcinoma (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.</p><p><strong>Key findings: </strong>In oral squamous cell carcinoma, 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 tumors 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.</p><p><strong>Significance: </strong>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 CDDP. TMEM30A is a potential gene target for CDDP anti-tumor activity in OSCC.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2000,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The effect of m6A methyltransferase METTL3 mediated TMEM30A regulation on tumor energy metabolism and cisplatin anti-tumor activity in oral squamous cell carcinoma.\",\"authors\":\"Wei Yuan, Shaobo Ouyang, Qiaoli Lv, Lan Liao\",\"doi\":\"10.1016/j.lfs.2024.123122\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Aims: </strong>Cisplatin (CDDP) 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 CDDP weakens its therapeutic effect. There is still limited research on the effect of METTL3-mediated methylation of m6A on CDDP sensitivity in oral squamous cell carcinoma (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.</p><p><strong>Key findings: </strong>In oral squamous cell carcinoma, 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 tumors 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.</p><p><strong>Significance: </strong>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 CDDP. TMEM30A is a potential gene target for CDDP anti-tumor activity in OSCC.</p>\",\"PeriodicalId\":18122,\"journal\":{\"name\":\"Life sciences\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.2000,\"publicationDate\":\"2024-10-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Life sciences\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.lfs.2024.123122\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Life sciences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.lfs.2024.123122","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
The effect of m6A methyltransferase METTL3 mediated TMEM30A regulation on tumor energy metabolism and cisplatin anti-tumor activity in oral squamous cell carcinoma.
Aims: Cisplatin (CDDP) 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 CDDP weakens its therapeutic effect. There is still limited research on the effect of METTL3-mediated methylation of m6A on CDDP sensitivity in oral squamous cell carcinoma (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.
Key findings: In oral squamous cell carcinoma, 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 tumors 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.
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 CDDP. TMEM30A is a potential gene target for CDDP anti-tumor activity in OSCC.
期刊介绍:
Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed.
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