CircARHGAP12 promotes nasopharyngeal carcinoma migration and invasion via ezrin-mediated cytoskeletal remodeling

CircARHGAP12 通过 ezrin 介导的细胞骨架重塑促进鼻咽癌迁移和侵袭

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作者:Chunmei Fan, Hongke Qu, Fang Xiong, Yanyan Tang, Ting Tang, Lishen Zhang, Yongzhen Mo, Xiayu Li, Can Guo, Shanshan Zhang, Zhaojian Gong, Zheng Li, Bo Xiang, Hao Deng, Ming Zhou, Qianjin Liao, Yujuan Zhou, Xiaoling Li, Yong Li, Guiyuan Li, Fuyan Wang, Zhaoyang Zeng

Abstract

An increasing number of studies have shown that circular RNAs (circRNAs) play important roles in malignant tumor initiation and progression; however, many circRNAs are yet unidentified, and the role of circRNAs in nasopharyngeal carcinoma (NPC) is unclear. Using RNA sequencing, we discovered a novel circRNA, termed circARHGAP12, that was processed from the pre-mRNA of the ARHGAP12 gene. CircARHGAP12 was significantly upregulated in NPC tissues and cell lines and promoted NPC cell migration and invasion. Overexpression or knockdown experiments revealed that circARHGAP12 regulates the expression of cytoskeletal remodeling-related proteins EZR, TPM3, and RhoA. CircARHGAP12 was found to bind directly to the 3' UTR of EZR mRNA and promote its stability; moreover, EZR protein interacted with TPM3 and RhoA and formed a complex to promote NPC cell invasion and metastasis. This study identified the novel circRNA circARHGAP12, characterized its biological function and mechanism, and increased our understanding of circRNAs in NPC pathogenesis. In particular, circARHGAP12 was found to promote the malignant biological phenotype of NPC via cytoskeletal remodeling, thus providing a clue for targeted therapy of NPC.

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