CircARHGAP12 promotes nasopharyngeal carcinoma migration and invasion via ezrin-mediated cytoskeletal remodeling
CircARHGAP12 promotes nasopharyngeal carcinoma migration and invasion via ezrin-mediated cytoskeletal remodeling
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DOI：
10.1016/j.canlet.2020.09.006
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发表时间：
2021-01-01
期刊：
影响因子：
9.7
通讯作者：
Zeng, Zhaoyang
中科院分区：
文献类型：
--
作者：
Fan, Chunmei;Qu, Hongke;Zeng, Zhaoyang
越来越多的研究表明，环状rna （circRNAs）在恶性肿瘤的发生和发展中起着重要作用；然而，许多circrna尚未被识别，circrna在鼻咽癌（NPC）中的作用尚不清楚。通过RNA测序，我们发现了一种新的环状RNA，称为circARHGAP12，它是由ARHGAP12基因的前mrna加工而成的。CircARHGAP12在鼻咽癌组织和细胞系中显著上调，促进鼻咽癌细胞迁移和侵袭。过表达或敲低实验显示circARHGAP12调节细胞骨架重塑相关蛋白EZR、TPM3和RhoA的表达。发现CircARHGAP12直接结合到EZR mRNA的3 ' UTR上，促进其稳定性；此外，EZR蛋白与TPM3、RhoA相互作用形成复合物，促进鼻咽癌细胞侵袭转移。本研究鉴定了新的circRNA circARHGAP12，并对其生物学功能和机制进行了表征，增加了我们对circRNA在NPC发病机制中的认识。特别是circARHGAP12通过细胞骨架重塑促进NPC的恶性生物学表型，为NPC的靶向治疗提供了线索。
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.