RETRACTED ARTICLE: N6-methyladenosine modification of circMARK2 enhances cytoplasmic export and stabilizes LIN28B, contributing to the progression of Wilms tumor
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Le résumé fourni par la source
Abstract Background The potential involvement of circular RNAs (circRNAs) and N6-methyladenosine (m6A) modification in the progression of Wilms tumor (WT) has not been fully elucidated. This study investigates the regulatory mechanisms and clinical significance of m6A-modified circMARK2 and its role in WT progression. Methods We identified dysregulated circRNAs through deep sequencing and validated their expression by qRT-PCR in WT tissues. The biological functions of circMARK2 were assessed using clone formation, transwell migration, and orthotopic animal models. To dissect the underlying mechanisms, we employed RNA immunoprecipitation, RNA pull-down, dual-luciferase reporter assays, Western blotting, and immunofluorescence and immunohistochemical staining. Results CircMARK2, upregulated in WT tissues, was found to be m6A-modified and promoted cytoplasmic export. It facilitated WT progression by stabilizing LIN28B mRNA through the circMARK2/IGF2BP2 interaction. In vitro and in vivo studies demonstrated that circMARK2 enhances the malignant behavior of WT cells. Clinically, higher circMARK2 levels in tumor tissues of WT patients were linked to increased tumor aggressiveness and reduced survival rates. Conclusions Our study provides the first comprehensive evidence that m6A-modified circMARK2 contributes to WT progression by enhancing LIN28B mRNA stability, promoting cellular aggressiveness. CircMARK2 emerges as a potential biomarker for prognosis and a promising target for therapeutic intervention in WT, underscoring the clinical relevance of m6A modification in pediatric renal cancer.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- RETRACTED ARTICLE: N6-methyladenosine modification of circMARK2 enhances cytoplasmic export and stabilizes LIN28B, contributing to the progression of Wilms tumor
- Date Crossref
- 11/07/2024
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Guangzhou Medical University Department of Urology pays non établi dans la noticeUniversité ou école supérieure
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Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease pays non établi dans la noticeStructure de recherche
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Sun Yat-sen University Department of Urology pays non établi dans la noticeUniversité ou école supérieure
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Chinese Academy of Sciences pays non établi dans la noticeOrganisme public
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Wuhan Institute of Virology pays non établi dans la noticeStructure de recherche
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Guangzhou Women and Children Medical Center pays non établi dans la noticeÉtablissement de santé
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State Key Laboratory of Virology pays non établi dans la noticeStructure de recherche
Department of Urology — Guangzhou Medical University, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease et Department of Urology — Sun Yat-sen University, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.