NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, PR China; The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medicine Sciences, Central South University, Changsha, Hunan, PR China; Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, PR China.
The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute and School of Basic Medicine Sciences, Central South University, Changsha, Hunan, PR China.
Cancer Lett. 2021 Jan 1;496:41-56. doi: 10.1016/j.canlet.2020.09.006. Epub 2020 Sep 12.
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.
越来越多的研究表明环状 RNA（circRNA）在恶性肿瘤的发生和发展中发挥重要作用；然而，许多 circRNA 尚未被鉴定，circRNA 在鼻咽癌（NPC）中的作用尚不清楚。我们通过 RNA 测序发现了一种新型的环状 RNA，称为 circARHGAP12，它是从 ARHGAP12 基因的前体 mRNA 中加工而来的。circARHGAP12 在 NPC 组织和细胞系中显著上调，并促进 NPC 细胞迁移和侵袭。过表达或敲低实验表明，circARHGAP12 调节细胞骨架重塑相关蛋白 EZR、TPM3 和 RhoA 的表达。研究发现 circARHGAP12 直接与 EZR mRNA 的 3'UTR 结合，促进其稳定性；此外，EZR 蛋白与 TPM3 和 RhoA 相互作用形成复合物，促进 NPC 细胞侵袭和转移。本研究鉴定了新型环状 RNA circARHGAP12，阐明了其生物学功能和机制，加深了我们对 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。
