南方医科大学学报2025，Vol.45Issue(11)：2320-2329,10.DOI:10.12122/j.issn.1673-4254.2025.11.04
circ_EPHB4协同YTHDF3通过N6-甲基腺苷依赖性稳定Wnt3促进胶质瘤进展
circ_EPHB4 synergizes with YTHDF3 to promote glioma progression via m6 A-dependent stabilization of Wnt3
摘要
Abstract
Objective To investigate the oncogenic role of circular RNA circ_EPHB4 in glioma and its molecular mechanism.Methods Microarray analysis was performed to identify the differentially expressed circRNAs in glioma tissues.The effects of circ_EPHB4 on glioma cell migration,invasion and epithelial-mesenchymal transition(EMT)in vitro and tumorigenicity in vivo were assessed using scratch wound healing assay,Transwell invasion assay and nude mouse models bearing subcutaneous tumors.RNA immunoprecipitation(RIP),RNA stability assays,and gene overexpression and silencing techniques were employed to validate the synergistic regulatory effect of circ_EPHB4 and the N6-methyladenosine(m6A)reader protein YTHDF3 on Wnt3 expression.Results Circ_EPHB4 was significantly overexpressed by 2.3 folds(|log2FC|=1.2,P<0.01)in glioma tissues compared to the adjacent tissues,and by 2.5 folds in glioma cell line U373 compared to normal cells(P<0.001).Overexpression of circ_EPHB4 significantly enhanced migration and invasion of glioma cells,and promoted the expressions of EMT markers N-cadherin and vimentin.In the tumor-bearing mouse models,the tumor volume in circ_EPHB4 overexpression group was significantly greater than that in the control group,and the lung metastatic foci increased by 4.2 folds.Overexpression of circ_EPHB4 promoted oncogenesis by upregulating Wnt3 expression,while YTHDF3 extended the half-life of Wnt3 mRNA in an m6A-dependent manner.Simultaneous knockdown of circ_EPHB4 and YTHDF3 resulted in an obvious reduction of Wnt3 mRNA expression by up to 47%compared to its level following knocking down either circ_EPHB4 or YTHDF3 alone.Conclusion Circ_EPHB4 and YTHDF3 promote glioma progression by jointly targeting the Wnt3 signaling pathway,which may provide a new therapeutic strategy for gliomas.关键词
circ_EPHB4/N6-甲基腺苷/YTHDF3/Wnt3/胶质瘤Key words
circ_EPHB4/m6A/YTHDF3/Wnt3/glioma引用本文复制引用
金晨,刘景平,刘博,费喜云,廖宇翔..circ_EPHB4协同YTHDF3通过N6-甲基腺苷依赖性稳定Wnt3促进胶质瘤进展[J].南方医科大学学报,2025,45(11):2320-2329,10.基金项目
湖南省青年自然科学基金(202140998) （202140998）
湖南省自然科学基金(2025JJ50742) （2025JJ50742）
