Basic Research

CircMYCBP2 enhances the formation of lymphovascular invasion of bladder cancer

  • Daiyin LIU ,
  • Qiuyan LI ,
  • Changhao. CHEN
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  • Department of Urology,Sun Yat?sen Memorial Hospital,Sun Yat?sen University,Guangzhou 510030,Guangdong,China
    *.Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation,State Key Laboratory of Oncology in South China,Guangzhou 510030,Guangdong,China

Received date: 2025-03-20

  Online published: 2025-04-30

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 formation 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 experiments 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.

Cite this article

Daiyin LIU , Qiuyan LI , Changhao. CHEN . CircMYCBP2 enhances the formation of lymphovascular invasion of bladder cancer[J]. The Journal of Practical Medicine, 2025 , 41(8) : 1139 -1148 . DOI: 10.3969/j.issn.1006-5725.2025.08.008

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