RETRACTED ARTICLE: N6-methyladenosine modification of circMARK2 enhances cytoplasmic export and stabilizes LIN28B, contributing to the progression of Wilms tumor

作者：Guannan Shu, Zhao Zhang, Tianxin Zhao, Changmi Deng, Jiangquan Zhu, Yufeng Han, Minyu Chen, Jiajia Jing, Gaochen Bai, Dian Li, Feng Li, Jing He, Wen Fu, Guochang Liu · 发表于：Journal of Experimental & Clinical Cancer Research · 年份：2024 · DOI：10.1186/s13046-024-03113-9 · 被引用次数：5 · 研究领域：Circular RNAs in diseases、Mechanisms of cancer metastasis、Cancer Mechanisms and Therapy

Abstract Background The potential involvement of circular RNAs (circRNAs) and N 6 -methyladenosine (m 6 A) modification in the progression of Wilms tumor (WT) has not been fully elucidated. This study investigates the regulatory mechanisms and clinical significance of m 6 A-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 m 6 A-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 m 6 A-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 tar...