新近发现的证据表明环状RNA（circRNAs）参与了癌症转移。深入研究circRNAs在口腔鳞状细胞癌（OSCC）中的作用，可能为了解推动转移的机制和潜在治疗靶点提供线索。在这里，我们确定了一种名为circFNDC3B的circRNA，该circRNA在OSCC中显著上调，并与淋巴结（LN）转移呈正相关。体外和体内功能实验表明，circFNDC3B加速了OSCC细胞的迁移和侵袭，以及人脐静脉内皮细胞（HUVEC）和人淋巴内皮细胞（HLEC）的管形成能力。机制上，circFNDC3B通过MMD2 E3连接酶调节RNA结合蛋白FUS的泛素化和HIF1A的脱泛素化，促进VEGFA 转录，从而增强血管生成。与此同时，circFNDC3B吸附miR-181c-5p，上调SERPINE1和PROX1，促进OSCC细胞的上皮间质转化（EMT）或部分EMT（p-EMT），并促进淋巴管生成，加速淋巴结转移。总的来说，这些发现揭示了circFNDC3B在编排癌细胞转移性质和血管形成方面的机制作用，表明circFNDC3B可能是减少OSCC转移的潜在靶点。

Emerging evidence has demonstrated that circular RNAs (circRNAs) are involved in cancer metastasis. Further elucidation of the role of circRNAs in oral squamous cell carcinoma (OSCC) could provide insights into mechanisms driving metastasis and potential therapeutic targets. Here, we identify a circRNA, circFNDC3B, that is significantly upregulated in OSCC and is positively associated with lymph node (LN) metastasis. In vitro and in vivo functional assays showed that circFNDC3B accelerated the migration and invasion of OSCC cells and the tube-forming capacity of human umbilical vein endothelial cells (HUVEC) and human lymphatic endothelial cells (HLEC). Mechanistically, circFNDC3B regulated ubiquitylation of the RNA-binding protein FUS and the deubiquitylation of HIF1A through the E3 ligase MDM2 to promote VEGFA transcription, thereby enhancing angiogenesis. Meanwhile, circFNDC3B sequestered miR-181c-5p to upregulate SERPINE1 and PROX1, which drove epithelial-mesenchymal transition (EMT) or partial-EMT (p-EMT) in OSCC cells and promoted lymphangiogenesis to accelerate lymph node metastasis. Overall, these findings uncovered the mechanistic role of circFNDC3B in orchestrating cancer cell metastatic properties and vasculature formation, suggesting circFNDC3B could be a potential target to reduce OSCC metastasis.