Wangyang Meng, Han Xiao, Rong Zhao, Jiaping Chen, Yangwei Wang, Peiyuan Mei, Hecheng Li, Yongde Liao
{"title":"METTL3 通过增强 CYP19A1 的翻译和雌激素的合成来促进 NSCLC 转移。","authors":"Wangyang Meng, Han Xiao, Rong Zhao, Jiaping Chen, Yangwei Wang, Peiyuan Mei, Hecheng Li, Yongde Liao","doi":"10.1186/s13578-024-01194-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>METTL3 plays a significant role as a catalytic enzyme in mediating N6-methyladenosine (m<sup>6</sup>A) modification, and its importance in tumour progression has been extensively studied in recent years. However, the precise involvement of METTL3 in the regulation of translation in non-small cell lung cancer (NSCLC) remains unclear.</p><p><strong>Results: </strong>Here we discovered by clinical investigation that METTL3 expression is correlated with NSCLC metastasis. Ablation of METTL3 in NSCLC cells inhibits invasion and metastasis in vitro and in vivo. Subsequently, through translatomics data mining and experimental validation, we demonstrated that METTL3 enhances the translation of aromatase (CYP19A1), a key enzyme in oestrogen synthesis, thereby promoting oestrogen production and mediating the invasion and metastasis of NSCLC. Mechanistically, METTL3 interacts with translation initiation factors and binds to CYP19A1 mRNA, thus enhancing the translation efficiency of CYP19A1 in an m<sup>6</sup>A-dependent manner. Pharmacological inhibition of METTL3 enzymatic activity or translation initiation factor eIF4E abolishes CYP19A1 protein synthesis.</p><p><strong>Conclusions: </strong>Our findings indicate the crucial role of METTL3-mediated translation regulation in NSCLC and reveal the significance of METTL3/eIF4E/CYP19A1 signaling as a promising therapeutic target for anti-metastatic strategies against NSCLC.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"14 1","pages":"10"},"PeriodicalIF":6.1000,"publicationDate":"2024-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10795463/pdf/","citationCount":"0","resultStr":"{\"title\":\"METTL3 drives NSCLC metastasis by enhancing CYP19A1 translation and oestrogen synthesis.\",\"authors\":\"Wangyang Meng, Han Xiao, Rong Zhao, Jiaping Chen, Yangwei Wang, Peiyuan Mei, Hecheng Li, Yongde Liao\",\"doi\":\"10.1186/s13578-024-01194-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>METTL3 plays a significant role as a catalytic enzyme in mediating N6-methyladenosine (m<sup>6</sup>A) modification, and its importance in tumour progression has been extensively studied in recent years. However, the precise involvement of METTL3 in the regulation of translation in non-small cell lung cancer (NSCLC) remains unclear.</p><p><strong>Results: </strong>Here we discovered by clinical investigation that METTL3 expression is correlated with NSCLC metastasis. Ablation of METTL3 in NSCLC cells inhibits invasion and metastasis in vitro and in vivo. Subsequently, through translatomics data mining and experimental validation, we demonstrated that METTL3 enhances the translation of aromatase (CYP19A1), a key enzyme in oestrogen synthesis, thereby promoting oestrogen production and mediating the invasion and metastasis of NSCLC. Mechanistically, METTL3 interacts with translation initiation factors and binds to CYP19A1 mRNA, thus enhancing the translation efficiency of CYP19A1 in an m<sup>6</sup>A-dependent manner. Pharmacological inhibition of METTL3 enzymatic activity or translation initiation factor eIF4E abolishes CYP19A1 protein synthesis.</p><p><strong>Conclusions: </strong>Our findings indicate the crucial role of METTL3-mediated translation regulation in NSCLC and reveal the significance of METTL3/eIF4E/CYP19A1 signaling as a promising therapeutic target for anti-metastatic strategies against NSCLC.</p>\",\"PeriodicalId\":49095,\"journal\":{\"name\":\"Cell and Bioscience\",\"volume\":\"14 1\",\"pages\":\"10\"},\"PeriodicalIF\":6.1000,\"publicationDate\":\"2024-01-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10795463/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell and Bioscience\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1186/s13578-024-01194-9\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell and Bioscience","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s13578-024-01194-9","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
METTL3 drives NSCLC metastasis by enhancing CYP19A1 translation and oestrogen synthesis.
Background: METTL3 plays a significant role as a catalytic enzyme in mediating N6-methyladenosine (m6A) modification, and its importance in tumour progression has been extensively studied in recent years. However, the precise involvement of METTL3 in the regulation of translation in non-small cell lung cancer (NSCLC) remains unclear.
Results: Here we discovered by clinical investigation that METTL3 expression is correlated with NSCLC metastasis. Ablation of METTL3 in NSCLC cells inhibits invasion and metastasis in vitro and in vivo. Subsequently, through translatomics data mining and experimental validation, we demonstrated that METTL3 enhances the translation of aromatase (CYP19A1), a key enzyme in oestrogen synthesis, thereby promoting oestrogen production and mediating the invasion and metastasis of NSCLC. Mechanistically, METTL3 interacts with translation initiation factors and binds to CYP19A1 mRNA, thus enhancing the translation efficiency of CYP19A1 in an m6A-dependent manner. Pharmacological inhibition of METTL3 enzymatic activity or translation initiation factor eIF4E abolishes CYP19A1 protein synthesis.
Conclusions: Our findings indicate the crucial role of METTL3-mediated translation regulation in NSCLC and reveal the significance of METTL3/eIF4E/CYP19A1 signaling as a promising therapeutic target for anti-metastatic strategies against NSCLC.
期刊介绍：
Cell and Bioscience, the official journal of the Society of Chinese Bioscientists in America, is an open access, peer-reviewed journal that encompasses all areas of life science research.
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