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Updated: Jun 9, 2025

Methyl-binding DNA capture Sequencing for Patient Tissues
Published on: October 31, 2016
SNORD99 promotes endometrial cancer development by inhibiting GSDMD-mediated pyroptosis through 2'-O-methylation
Jing-Yuan Xian1,2, Wu Wu1,2, Xi Chen1,2
1Department 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-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Abstract:
Eukaryotic cells possess multiple mechanisms of self-destruction, including pyroptosis and necroptosis. Pyroptosis is a type of programmed cell death characterized by cellular rupture and linked to inflammation. SnoRNA, a small non-coding RNA in the nucleolus, can dysregulate specific RNAs through 2'-O-methylation, contributing to tumorigenesis. Our StarBase and qRT-PCR analysis revealed SNORD99 upregulation in endometrial cancer (EC) tissue compared to normal tissue, suggesting its role in pathogenesis. SNORD99 overexpression enhanced migration and proliferation of EC cells, while ASO-mediated suppression reduced malignant cell spread and division. RNA-seq and base-comparing analysis identified GSDMD's differential expression upon SNORD99 overexpression, forming the SNORD99-FBL RNP complex. RTL-P experiments showed SNORD99 increased GSDMD's 2'-O-methylation. SNORD99 reduced GSDMD, caspase-1, and NLRP3 protein levels, implicating its role in pyroptosis. Optical and electron microscopy confirmed enhanced pyroptosis features. In summary, SNORD99 modifies GSDMD via 2'-O-methylation, suppressing pyroptosis and promoting EC progression. Developing pyroptosis-inducing drugs may offer new cancer treatment avenues.
Insights
SNORD99, a small nucleolar RNA, promotes endometrial cancer by suppressing pyroptosis. It methylates GSDMD, inhibiting cell death and enhancing tumor growth, suggesting new therapeutic targets.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Eukaryotic cells have self-destruction mechanisms like pyroptosis.
- Small nucleolar RNAs (snoRNAs) can regulate gene expression and are implicated in cancer.
- Pyroptosis is a pro-inflammatory programmed cell death pathway crucial in immunity and disease.
Purpose of the Study:
- To investigate the role of SNORD99 in endometrial cancer (EC) pathogenesis.
- To elucidate the molecular mechanism by which SNORD99 influences cell death pathways.
- To explore SNORD99 as a potential therapeutic target for EC.
Main Methods:
- StarBase and qRT-PCR for SNORD99 expression analysis in EC tissues.
- Cell proliferation, migration assays, and ASO-mediated knockdown in EC cells.
- RNA-sequencing, RNP complex formation analysis, RTL-P, Western blotting, and microscopy to study SNORD99-GSDMD interaction and pyroptosis.
Main Results:
- SNORD99 was significantly upregulated in EC tissues and promoted EC cell migration and proliferation.
- SNORD99 overexpression led to the formation of a SNORD99-FBL RNP complex and increased GSDMD 2'-O-methylation.
- SNORD99 suppressed pyroptosis by reducing GSDMD, caspase-1, and NLRP3 protein levels, thereby promoting EC progression.
Conclusions:
- SNORD99 promotes endometrial cancer progression by inhibiting pyroptosis through GSDMD 2'-O-methylation.
- Targeting SNORD99 or enhancing pyroptosis could be a viable therapeutic strategy for EC.
- This study reveals a novel mechanism linking snoRNAs to cell death regulation in cancer.
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