Jie Chen, Henglan Wu, Ting Zuo, Jianming Wu, Zhiheng Chen
{"title":"METTL3 介导的 MMP9 mRNA 的 N6-甲基腺苷修饰可促进结直肠癌的增殖和迁移。","authors":"Jie Chen, Henglan Wu, Ting Zuo, Jianming Wu, Zhiheng Chen","doi":"10.3892/or.2024.8842","DOIUrl":null,"url":null,"abstract":"<p><p>N6‑methyladenosine (m<sup>6</sup>A) is the predominant chemical modification of eukaryotic mRNA, dynamically mediated by the RNA methyltransferase, methyltransferase-like 3 (METTL3). m<sup>6</sup>A modification plays a critical role in cancer progression through post‑transcriptional regulation in various types of cancer. However, the role of METTL3 and its associated m<sup>6</sup>A modification in colorectal tumorigenesis remains to be fully elucidated. In the present study, it was demonstrated that METTL3 expression and the m<sup>6</sup>A levels were both upregulated in colorectal cancer (CRC) and positively associated with clinical progression, based on the bioinformatics analysis of cancer databases. Furthermore, knockdown and overexpression of METTL3 notably affected CRC cell viability, apoptosis and migration <i>in vitro</i>. Similarly, xenograft animal models confirmed that METTL3 promoted CRC tumorigenicity <i>in vivo</i>. Mechanistically, it was revealed that the m<sup>6</sup>A modification of matrix metallopeptidase 9 (MMP9) mRNA mediated by METTL3 promoted its expression in CRC by decreasing its degradation. Collectively, the findings of the present study suggested that the METTL3/MMP9 axis could serve as a novel promising therapeutic candidate for CRC.</p>","PeriodicalId":19527,"journal":{"name":"Oncology reports","volume":"53 1","pages":""},"PeriodicalIF":3.8000,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11576960/pdf/","citationCount":"0","resultStr":"{\"title\":\"METTL3‑mediated N6‑methyladenosine modification of MMP9 mRNA promotes colorectal cancer proliferation and migration.\",\"authors\":\"Jie Chen, Henglan Wu, Ting Zuo, Jianming Wu, Zhiheng Chen\",\"doi\":\"10.3892/or.2024.8842\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>N6‑methyladenosine (m<sup>6</sup>A) is the predominant chemical modification of eukaryotic mRNA, dynamically mediated by the RNA methyltransferase, methyltransferase-like 3 (METTL3). m<sup>6</sup>A modification plays a critical role in cancer progression through post‑transcriptional regulation in various types of cancer. However, the role of METTL3 and its associated m<sup>6</sup>A modification in colorectal tumorigenesis remains to be fully elucidated. In the present study, it was demonstrated that METTL3 expression and the m<sup>6</sup>A levels were both upregulated in colorectal cancer (CRC) and positively associated with clinical progression, based on the bioinformatics analysis of cancer databases. Furthermore, knockdown and overexpression of METTL3 notably affected CRC cell viability, apoptosis and migration <i>in vitro</i>. Similarly, xenograft animal models confirmed that METTL3 promoted CRC tumorigenicity <i>in vivo</i>. Mechanistically, it was revealed that the m<sup>6</sup>A modification of matrix metallopeptidase 9 (MMP9) mRNA mediated by METTL3 promoted its expression in CRC by decreasing its degradation. Collectively, the findings of the present study suggested that the METTL3/MMP9 axis could serve as a novel promising therapeutic candidate for CRC.</p>\",\"PeriodicalId\":19527,\"journal\":{\"name\":\"Oncology reports\",\"volume\":\"53 1\",\"pages\":\"\"},\"PeriodicalIF\":3.8000,\"publicationDate\":\"2025-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11576960/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Oncology reports\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3892/or.2024.8842\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/11/14 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oncology reports","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3892/or.2024.8842","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/11/14 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
METTL3‑mediated N6‑methyladenosine modification of MMP9 mRNA promotes colorectal cancer proliferation and migration.
N6‑methyladenosine (m6A) is the predominant chemical modification of eukaryotic mRNA, dynamically mediated by the RNA methyltransferase, methyltransferase-like 3 (METTL3). m6A modification plays a critical role in cancer progression through post‑transcriptional regulation in various types of cancer. However, the role of METTL3 and its associated m6A modification in colorectal tumorigenesis remains to be fully elucidated. In the present study, it was demonstrated that METTL3 expression and the m6A levels were both upregulated in colorectal cancer (CRC) and positively associated with clinical progression, based on the bioinformatics analysis of cancer databases. Furthermore, knockdown and overexpression of METTL3 notably affected CRC cell viability, apoptosis and migration in vitro. Similarly, xenograft animal models confirmed that METTL3 promoted CRC tumorigenicity in vivo. Mechanistically, it was revealed that the m6A modification of matrix metallopeptidase 9 (MMP9) mRNA mediated by METTL3 promoted its expression in CRC by decreasing its degradation. Collectively, the findings of the present study suggested that the METTL3/MMP9 axis could serve as a novel promising therapeutic candidate for CRC.
期刊介绍:
Oncology Reports is a monthly, peer-reviewed journal devoted to the publication of high quality original studies and reviews concerning a broad and comprehensive view of fundamental and applied research in oncology, focusing on carcinogenesis, metastasis and epidemiology.