{"title":"WTAP-mediated m6A modification regulates NLRP3/Caspase-1/GSDMD to inhibit pyroptosis and exacerbate colorectal cancer.","authors":"Anwei Mo, Huaiwen Wang","doi":"10.1080/17520363.2024.2416886","DOIUrl":null,"url":null,"abstract":"<p><p><b>Aim:</b> Wilms' tumor 1-associating protein (WTAP), plays a part in colorectal cancer (CRC) progression. However, it is not yet known how WTAP affects cancer progression by influencing leukocyte rich repeat containing proteins (NLR) - family members 3 (NLRP3) - related inflammasomes.<b>Materials & methods:</b> We first validated the expression of WTAP in CRC at the tissue and cellular levels. Subsequently, by transfecting si-NC and si-WTAP into cells, we verified functions of WTAP in proliferation, invasion, migration and apoptosis of CRC cells. Finally, we analyzed the N6-methyladenosine (m6A) modification of NLRP3 by WTAP using methylated RNA immunoprecipitation (MeRIP)-qPCR technology, confirming that WTAP mediated the repression of NLRP3 inflammasome and the malignant progression of tumor cells.<b>Results:</b> WTAP was substantially upregulated in CRC tissues and cells. WTAP reinforced the migration, proliferation and invasion ability of CRC cells, and repressed apoptosis. Mechanistically, WTAP mediated the m6A modification of NLRP3, which suppressed the expression of NLRP3 and dampened the NLRP3/Caspase-1/GSDMD axis activation as well as pyroptosis, thereby facilitating the malignant progression of CRC.<b>Conclusion:</b> WTAP mediates m6A modification to modulate the repression of the NLRP3/Caspase-1/GSDMD axis in pyroptosis, reinforcing the malignant progression of CRC.</p>","PeriodicalId":9182,"journal":{"name":"Biomarkers in medicine","volume":" ","pages":"1-11"},"PeriodicalIF":1.9000,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomarkers in medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17520363.2024.2416886","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Aim: Wilms' tumor 1-associating protein (WTAP), plays a part in colorectal cancer (CRC) progression. However, it is not yet known how WTAP affects cancer progression by influencing leukocyte rich repeat containing proteins (NLR) - family members 3 (NLRP3) - related inflammasomes.Materials & methods: We first validated the expression of WTAP in CRC at the tissue and cellular levels. Subsequently, by transfecting si-NC and si-WTAP into cells, we verified functions of WTAP in proliferation, invasion, migration and apoptosis of CRC cells. Finally, we analyzed the N6-methyladenosine (m6A) modification of NLRP3 by WTAP using methylated RNA immunoprecipitation (MeRIP)-qPCR technology, confirming that WTAP mediated the repression of NLRP3 inflammasome and the malignant progression of tumor cells.Results: WTAP was substantially upregulated in CRC tissues and cells. WTAP reinforced the migration, proliferation and invasion ability of CRC cells, and repressed apoptosis. Mechanistically, WTAP mediated the m6A modification of NLRP3, which suppressed the expression of NLRP3 and dampened the NLRP3/Caspase-1/GSDMD axis activation as well as pyroptosis, thereby facilitating the malignant progression of CRC.Conclusion: WTAP mediates m6A modification to modulate the repression of the NLRP3/Caspase-1/GSDMD axis in pyroptosis, reinforcing the malignant progression of CRC.
期刊介绍：
Biomarkers are physical, functional or biochemical indicators of physiological or disease processes. These key indicators can provide vital information in determining disease prognosis, in predicting of response to therapies, adverse events and drug interactions, and in establishing baseline risk. The explosion of interest in biomarker research is driving the development of new predictive, diagnostic and prognostic products in modern medical practice, and biomarkers are also playing an increasingly important role in the discovery and development of new drugs. For the full utility of biomarkers to be realized, we require greater understanding of disease mechanisms, and the interplay between disease mechanisms, therapeutic interventions and the proposed biomarkers. However, in attempting to evaluate the pros and cons of biomarkers systematically, we are moving into new, challenging territory.
Biomarkers in Medicine (ISSN 1752-0363) is a peer-reviewed, rapid publication journal delivering commentary and analysis on the advances in our understanding of biomarkers and their potential and actual applications in medicine. The journal facilitates translation of our research knowledge into the clinic to increase the effectiveness of medical practice.
As the scientific rationale and regulatory acceptance for biomarkers in medicine and in drug development become more fully established, Biomarkers in Medicine provides the platform for all players in this increasingly vital area to communicate and debate all issues relating to the potential utility and applications.
Each issue includes a diversity of content to provide rounded coverage for the research professional. Articles include Guest Editorials, Interviews, Reviews, Research Articles, Perspectives, Priority Paper Evaluations, Special Reports, Case Reports, Conference Reports and Company Profiles. Review coverage is divided into themed sections according to area of therapeutic utility with some issues including themed sections on an area of topical interest.
Biomarkers in Medicine provides a platform for commentary and debate for all professionals with an interest in the identification of biomarkers, elucidation of their role and formalization and approval of their application in modern medicine. The audience for Biomarkers in Medicine includes academic and industrial researchers, clinicians, pathologists, clinical chemists and regulatory professionals.
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