实用医学杂志2025，Vol.41Issue(8)：1139-1148,10.DOI:10.3969/j.issn.1006-5725.2025.08.008
CircMYCBP2促进膀胱癌淋巴管癌栓形成的机制
CircMYCBP2 enhances the formation of lymphovascular invasion of bladder cancer
摘要
Abstract
Objective To investigate the role of circular RNA,circMYCBP2,which is highly expressed in lymph node(LN)metastatic bladder cancer(BCa)tissues,in enhancing BCa cell adhesion and mediating lymphovascular invasion(LVI),and to evaluate its clinical relevance and potential therapeutic value.Methods High-throughput sequencing identified circRNAs with high expression in LN metastatic BCa tissues.Further validation of their expression in bladder cancer tissues was conducted through clinical samples.The coding ability of circMYCBP2 was predicted by circBank bioinformatics website,and the encoded short peptide was detected by immunoprecipitation(co-IP)combined with silver staining and Western blot(WB).Then,by constructing BCa cells with overexpression and knockdown of circMYCBP2 in vitro,the invasive ability of BCa cells was verified by wound healing and transendothelial cell migration assays.The underlying mechanism of circMYCBP2 in the forma-tion of LVI was explored through RNA pulldown,qRT-PCR and WB.Results High-throughput sequencing and clinical sample validation confirmed that circMYCBP2 is highly expressed in LN metastatic BCa.In vitro experi-ments demonstrated that circMYCBP2 overexpression significantly enhanced BCa cell migration across lymphatic endothelial cells.Mechanistically,circMYCBP2 encodes the short peptide MYCBP2-227aa via an IRES-dependent mechanism by interacting with EIF3H.Overexpression of MYCBP2-227aa increased the mRNA stability of VCAM-1,thereby enhancing the invasive capacity of UM-UC-3 cells.Conclusions CircMYCBP2 encodes the short peptide MYCBP2-227aa through an EIF3H-mediated,IRES-dependent translation mechanism.MYCBP2-227aa regulates VCAM-1 expression and promotes the invasive behavior of BCa cells.Our findings elucidate the critical biological role and molecular mechanism of circMYCBP2 in the formation of LVI and LN metastasis of BCa,providing a potential biomarker and therapeutic target for early lymphatic metastasis in BCa.关键词
膀胱癌/淋巴管癌栓/circRNA翻译/内部核糖体进入位点Key words
bladder cancer/lymphovascular invasion/circRNA translation/IRES分类
临床医学引用本文复制引用
刘戴胤,李秋燕,陈长昊..CircMYCBP2促进膀胱癌淋巴管癌栓形成的机制[J].实用医学杂志,2025,41(8):1139-1148,10.基金项目
国家重点研发计划项目(编号:2022YFA1305500) （编号:2022YFA1305500）
国家自然科学基金优秀青年科学基金项目(编号:32322023) （编号:32322023）
