CircRNA FNIP1调控细胞侵袭性伪足形成促进鼻咽癌转移的作用及机制研究

肿瘤细胞侵袭性伪足在鼻咽癌转移中起着重要作用。我们在上一基金中已证明miR-16靶向FMNL1调控细胞侵袭伪足促进肿瘤转移。申请人应用circRNA芯片首次发现circFNIP1与鼻咽癌转移密切相关，预实验结果示敲除circRNA可减少细胞侵袭性伪足形成抑制鼻咽癌转移；敲除circFNIP1可靶向miR-16-2-3p下调FMNL1和MTA1的表达；RNA pull down实验发现circFNIP1与侵袭性伪足相关蛋白cortactin、cofilin相互作用。本项目针对“circFNIP1是否通过与cortactin、cofilin相互作用，经miR-16-2-3p/FMNL1/MTA1轴调控侵袭性伪足形成促进鼻咽细胞转移”这一科学问题，采用细胞、分子生物学及动物实验阐明circFNIP1促进侵袭性伪足形成促进鼻咽细胞转移的分子机制，将为鼻咽癌的诊治提供新的靶点。

Invidopodia formation plays a critical role in the invasion and metastasis of nasopharyngeal carcinoma (NPC). Previously, we found that miR-16 inhibits NPC cell metastasis by regulating FMNL1 expression. Recently, we performed circRNA microarray to identify the differentially expressed circRNA between NPC tissues with and without metastasis and found circRNA FNIP1 was significantly up-regulated in tissues with metastasis. We found silencing expression of circFNIP1 inhibit NPC cell metastasis by reducing invadopodia formation. Bioinformatic analysis found that miR-16-2-3p is the target miRNA of circFNIP1. Depletion of circFNIP1 potently suppressed expression of FMNL1 and MTA1. RNA pull down was applied to verify the interaction between circFNIP1 and invadopodia-related protein cortactin, cofilin. The aim of this study was to evaluate the mechanisms of circFNIP1 regulated invadopodia formation in metastasis process of NPC through miR-16-2-3p/FMNL1/MTA1 pathway by interacting with cortactin and cofilin. In this project, cell, molecular biology and animal experiments will be applied to verify and identify the function and mechanism of circFNIP1 enhancing NPC cell metastasis by regulating invadopodia formation. This study will provide new biomarkers and targets for the diagnosis and treatment of NPC.