Yongxu Su, Yanjia Hu, Binbin Qu, Rongchang Lei, Ge Guo
{"title":"METTL3 通过依赖 m6A-YTHDF2 下调 WEE1 促进 OSCC 进展","authors":"Yongxu Su, Yanjia Hu, Binbin Qu, Rongchang Lei, Ge Guo","doi":"10.1007/s12033-024-01165-y","DOIUrl":null,"url":null,"abstract":"<p><p>Oral squamous cell carcinoma (OSCC) is a common and highly lethal epithelial cancer. This study aimed to confirm the role of METTL3 in promoting OSCC and investigate its specific underlying mechanisms. Expression of the METTL3, YTH domain-containing family 2 (YTHDF2), and WEE1 were examined in normal oral epithelial cells and OSCC cells. Cell functions were examined after overexpressing WEE1 in OSCC cells. MeRIP-qPCR analysis was used to detect WEE1 m6A levels in HOK, SCC25, and CAL27 cells. WEE1 and its m6A levels were evaluated in OSCC cells by knocking down METTL3/YTHDF2, assessing the interaction between METTL3/YTHDF2 and WEE1. The impact of METTL3 and YTHDF2 downregulation on WEE1 mRNA stability was also investigated. The tumor weight and volume in a nude mouse model of OSCC after overexpression of WEE1 and YTHDF2 were measured. Expression of Ki-67 and WEE1 in OSCC tissue was detected using immunohistochemistry. Compared to normal oral epithelial cells, METTL3 and YTHDF2 were upregulated in OSCC cells, while WEE1 was downregulated, and there was a negative correlation between WEE1 and METTL3/YTHDF2 expression. WEE1 overexpression inhibited proliferation, invasion, and migration while promoting apoptosis in OSCC cells. METTL3 and YTHDF2 bound to WEE1 mRNA. METTL3/YTHDF2 knockdown increased WEE1 levels and WEE1 mRNA stability. METTL3 inhibition reduced WEE1 m6A levels. Inhibition of METTL3 weakened the interaction between YTHDF2 and WEE1 mRNA. In vivo, overexpression of WEE1 suppressed OSCC development, which was reversed by overexpression of YTHDF2. METTL3 facilitates the progression of OSCC through m6A-YTHDF2-dependent downregulation of WEE1.</p>","PeriodicalId":18865,"journal":{"name":"Molecular Biotechnology","volume":" ","pages":"1867-1879"},"PeriodicalIF":2.4000,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"METTL3 Promotes OSCC Progression by Down-Regulating WEE1 in a m6A-YTHDF2-Dependent Manner.\",\"authors\":\"Yongxu Su, Yanjia Hu, Binbin Qu, Rongchang Lei, Ge Guo\",\"doi\":\"10.1007/s12033-024-01165-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Oral squamous cell carcinoma (OSCC) is a common and highly lethal epithelial cancer. This study aimed to confirm the role of METTL3 in promoting OSCC and investigate its specific underlying mechanisms. Expression of the METTL3, YTH domain-containing family 2 (YTHDF2), and WEE1 were examined in normal oral epithelial cells and OSCC cells. Cell functions were examined after overexpressing WEE1 in OSCC cells. MeRIP-qPCR analysis was used to detect WEE1 m6A levels in HOK, SCC25, and CAL27 cells. WEE1 and its m6A levels were evaluated in OSCC cells by knocking down METTL3/YTHDF2, assessing the interaction between METTL3/YTHDF2 and WEE1. The impact of METTL3 and YTHDF2 downregulation on WEE1 mRNA stability was also investigated. The tumor weight and volume in a nude mouse model of OSCC after overexpression of WEE1 and YTHDF2 were measured. Expression of Ki-67 and WEE1 in OSCC tissue was detected using immunohistochemistry. Compared to normal oral epithelial cells, METTL3 and YTHDF2 were upregulated in OSCC cells, while WEE1 was downregulated, and there was a negative correlation between WEE1 and METTL3/YTHDF2 expression. WEE1 overexpression inhibited proliferation, invasion, and migration while promoting apoptosis in OSCC cells. METTL3 and YTHDF2 bound to WEE1 mRNA. METTL3/YTHDF2 knockdown increased WEE1 levels and WEE1 mRNA stability. METTL3 inhibition reduced WEE1 m6A levels. Inhibition of METTL3 weakened the interaction between YTHDF2 and WEE1 mRNA. In vivo, overexpression of WEE1 suppressed OSCC development, which was reversed by overexpression of YTHDF2. METTL3 facilitates the progression of OSCC through m6A-YTHDF2-dependent downregulation of WEE1.</p>\",\"PeriodicalId\":18865,\"journal\":{\"name\":\"Molecular Biotechnology\",\"volume\":\" \",\"pages\":\"1867-1879\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2025-05-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular Biotechnology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s12033-024-01165-y\",\"RegionNum\":4,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/5/14 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Biotechnology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12033-024-01165-y","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/14 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
METTL3 Promotes OSCC Progression by Down-Regulating WEE1 in a m6A-YTHDF2-Dependent Manner.
Oral squamous cell carcinoma (OSCC) is a common and highly lethal epithelial cancer. This study aimed to confirm the role of METTL3 in promoting OSCC and investigate its specific underlying mechanisms. Expression of the METTL3, YTH domain-containing family 2 (YTHDF2), and WEE1 were examined in normal oral epithelial cells and OSCC cells. Cell functions were examined after overexpressing WEE1 in OSCC cells. MeRIP-qPCR analysis was used to detect WEE1 m6A levels in HOK, SCC25, and CAL27 cells. WEE1 and its m6A levels were evaluated in OSCC cells by knocking down METTL3/YTHDF2, assessing the interaction between METTL3/YTHDF2 and WEE1. The impact of METTL3 and YTHDF2 downregulation on WEE1 mRNA stability was also investigated. The tumor weight and volume in a nude mouse model of OSCC after overexpression of WEE1 and YTHDF2 were measured. Expression of Ki-67 and WEE1 in OSCC tissue was detected using immunohistochemistry. Compared to normal oral epithelial cells, METTL3 and YTHDF2 were upregulated in OSCC cells, while WEE1 was downregulated, and there was a negative correlation between WEE1 and METTL3/YTHDF2 expression. WEE1 overexpression inhibited proliferation, invasion, and migration while promoting apoptosis in OSCC cells. METTL3 and YTHDF2 bound to WEE1 mRNA. METTL3/YTHDF2 knockdown increased WEE1 levels and WEE1 mRNA stability. METTL3 inhibition reduced WEE1 m6A levels. Inhibition of METTL3 weakened the interaction between YTHDF2 and WEE1 mRNA. In vivo, overexpression of WEE1 suppressed OSCC development, which was reversed by overexpression of YTHDF2. METTL3 facilitates the progression of OSCC through m6A-YTHDF2-dependent downregulation of WEE1.
期刊介绍：
Molecular Biotechnology publishes original research papers on the application of molecular biology to both basic and applied research in the field of biotechnology. Particular areas of interest include the following: stability and expression of cloned gene products, cell transformation, gene cloning systems and the production of recombinant proteins, protein purification and analysis, transgenic species, developmental biology, mutation analysis, the applications of DNA fingerprinting, RNA interference, and PCR technology, microarray technology, proteomics, mass spectrometry, bioinformatics, plant molecular biology, microbial genetics, gene probes and the diagnosis of disease, pharmaceutical and health care products, therapeutic agents, vaccines, gene targeting, gene therapy, stem cell technology and tissue engineering, antisense technology, protein engineering and enzyme technology, monoclonal antibodies, glycobiology and glycomics, and agricultural biotechnology.
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