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环状 RNA circCCNB1 通过结合并稳定 TJP1 mRNA 抑制鼻咽癌细胞的迁移和侵袭。

Circular RNA circCCNB1 inhibits the migration and invasion of nasopharyngeal carcinoma through binding and stabilizing TJP1 mRNA.

机构信息

NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, 410078, China.

Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, 410083, China.

出版信息

Sci China Life Sci. 2022 Nov;65(11):2233-2247. doi: 10.1007/s11427-021-2089-8. Epub 2022 Apr 21.

Abstract

Nasopharyngeal carcinoma (NPC) is a malignant tumor that usually occurs in people from Southeast Asia and Southern China. NPC is prone to migration and invasion, leading to poor prognosis. A large number of circular RNAs (circRNAs) exacerbate the process of metastasis in NPC; however, their underlying mechanisms remain unclear. We found that the circular RNA circCCNB1, encoded by the oncogene CCNB1, was downregulated in NPC biopsies and cell lines. In vitro assays show that circCCNB1 inhibits NPC cell migration and invasion. Moreover, circCCNB1 induces a protein, nuclear factor 90 (NF90), to bind and prolong the half-life of tight junction protein 1 (TJP1) mRNA. Upregulation of TJP1 enhances tight junctions between cancer cells and inhibits NPC cell migration and invasion. This study reveals a novel biological function of circCCNB1 in the migration and invasion of NPC by enhancing the tight junctions of cancer cells by binding to NF90 proteins and TJP1 mRNA, and may provide a potential therapeutic target for NPC.

摘要

鼻咽癌(NPC)是一种恶性肿瘤,通常发生在东南亚和中国南方地区的人群中。NPC 易发生迁移和侵袭,导致预后不良。大量的环状 RNA(circRNA)加剧了 NPC 的转移过程,但它们的潜在机制尚不清楚。我们发现,由癌基因 CCNB1 编码的环状 RNA circCCNB1 在 NPC 活检组织和细胞系中表达下调。体外实验表明 circCCNB1 抑制 NPC 细胞迁移和侵袭。此外,circCCNB1 诱导核因子 90(NF90)蛋白结合并延长紧密连接蛋白 1(TJP1)mRNA 的半衰期。TJP1 的上调增强了癌细胞之间的紧密连接,抑制了 NPC 细胞的迁移和侵袭。这项研究揭示了 circCCNB1 通过与 NF90 蛋白和 TJP1 mRNA 结合增强癌细胞的紧密连接,从而增强 NPC 迁移和侵袭的新的生物学功能,可能为 NPC 提供一个潜在的治疗靶点。

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