Fan Chunmei, Tan Fenghua, Wu Jie, Zeng Zhaoyang, Guo Wenjia, Huang He, Xiong Wei
NHC Key Laboratory of Carcinogenesis and Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Department of Histology and Embryology, Xiangya School of Medicine, Central South University, Changsha, China.
Mol Oncol. 2025 Jun;19(6):1876-1893. doi: 10.1002/1878-0261.13821. Epub 2025 Feb 18.
Nasopharyngeal carcinoma (NPC) is a kind of malignant tumor with high metastasis. Circular RNAs (circRNAs) are involved in tumor progression, but their functions and mechanisms are not well understood. Vasculogenic mimicry (VM) has been discovered as an alternative way to supply tumor nutrition and accelerate tumor progression, including NPC. We previously found that circCCNB1 (derived from cyclin B1) could inhibit the migration and invasion of NPC cells by binding to nuclear factor 90 (NF90), however, whether circCCNB1 has additional biological functions is still unclear. In this study, the effects of circCCNB1 binding to NF90 on the generation of miR-15b-5p and miR-7-1-3p were detected using qRT-PCR, western blotting, RNA pulldown, ribonucleoprotein immunoprecipitation and truncated experiments. VM formation assays were used to assess their biological functions. We found that circCCNB1 promoted the processing and generation of miR-15b-5p and miR-7-1-3p through competitive binding to NF90, thereby inhibiting the expression of calumenin (CALU), kinesin family member 1B (KIF1B), RNA polymerase III subunit G (POLR3G), ultimately decreasing the VM of NPC cells. This study not only reveals a new function of circCCNB1 in NPC, but also provides new insights for targeting angiogenesis therapy.
鼻咽癌（NPC）是一种具有高转移特性的恶性肿瘤。环状RNA（circRNAs）参与肿瘤进展，但其功能和机制尚不清楚。血管生成拟态（VM）已被发现是一种为肿瘤提供营养并加速肿瘤进展的替代途径，包括鼻咽癌。我们之前发现circCCNB1（源自细胞周期蛋白B1）可通过与核因子90（NF90）结合来抑制NPC细胞的迁移和侵袭，然而，circCCNB1是否具有其他生物学功能仍不清楚。在本研究中，使用qRT-PCR、蛋白质印迹、RNA下拉、核糖核蛋白免疫沉淀和截短实验检测了circCCNB1与NF90结合对miR-15b-5p和miR-7-1-3p生成的影响。采用VM形成实验评估它们的生物学功能。我们发现circCCNB1通过与NF90竞争性结合促进miR-15b-5p和miR-7-1-3p的加工和生成，从而抑制钙网蛋白（CALU）、驱动蛋白家族成员1B（KIF1B）、RNA聚合酶III亚基G（POLR3G）的表达，最终降低NPC细胞的VM。本研究不仅揭示了circCCNB1在鼻咽癌中的新功能，也为靶向血管生成治疗提供了新的见解。
