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Pyroptosis is a type of programmed cell death characterized by cellular rupture and linked to inflammation. SnoRNA, a small non\u2010coding RNA in the nucleolus, can dysregulate specific RNAs through 2'\u2010O\u2010methylation, contributing to tumorigenesis. Our StarBase and qRT\u2010PCR analysis revealed <jats:italic>SNORD99<\/jats:italic> upregulation in endometrial cancer (EC) tissue compared to normal tissue, suggesting its role in pathogenesis. <jats:italic>SNORD99<\/jats:italic> overexpression enhanced migration and proliferation of EC cells, while ASO\u2010mediated suppression reduced malignant cell spread and division. RNA\u2010seq and base\u2010comparing analysis identified GSDMD's differential expression upon <jats:italic>SNORD99<\/jats:italic> overexpression, forming the <jats:italic>SNORD99<\/jats:italic>\u2010FBL RNP complex. RTL\u2010P experiments showed <jats:italic>SNORD99<\/jats:italic> increased GSDMD's 2'\u2010O\u2010methylation. <jats:italic>SNORD99<\/jats:italic> reduced GSDMD, caspase\u20101, and NLRP3 protein levels, implicating its role in pyroptosis. Optical and electron microscopy confirmed enhanced pyroptosis features. In summary, <jats:italic>SNORD99<\/jats:italic> modifies GSDMD via 2'\u2010O\u2010methylation, suppressing pyroptosis and promoting EC progression. Developing pyroptosis\u2010inducing drugs may offer new cancer treatment avenues.<\/jats:p>","DOI":"10.1111\/jcmm.18500","type":"journal-article","created":{"date-parts":[[2024,6,22]],"date-time":"2024-06-22T10:53:57Z","timestamp":1719053637000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["<scp><i>SNORD99<\/i><\/scp> promotes endometrial cancer development by inhibiting <scp>GSDMD<\/scp>\u2010mediated pyroptosis through 2'\u2010O\u2010methylation modification"],"prefix":"10.1111","volume":"28","author":[{"given":"Jing\u2010yuan","family":"Xian","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Guangzhou Key Laboratory of Targeted Therapy for Gynecologic Oncology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, Guangdong\u2010Hong Kong\u2010Macao Greater Bay Area Higher Education Joint 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