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环状 RNA AGFG1 通过海绵吸附 miR-203 而上调 ZNF281 表达促进非小细胞肺癌 EMT 转移。

CircAGFG1 sponges miR-203 to promote EMT and metastasis of non-small-cell lung cancer by upregulating ZNF281 expression.

机构信息

Department of Thoracic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.

出版信息

Thorac Cancer. 2019 Aug;10(8):1692-1701. doi: 10.1111/1759-7714.13131. Epub 2019 Jun 27.

Abstract

The circRNA circAGFG1 is reported to be important in triple-negative breast cancer progression. However, the mechanism of circAGFG1 in non-small-cell lung cancer (NSCLC) remains unknown. In this study, expression of circAGFG1 was determined by real-time PCR in 20 pairs of NSCLC tissues and adjacent tissues. Next, functional experiments with circAGFG1 were performed in vitro to evaluate the role of circAGFG1 in tumor metastasis and growth. Meanwhile, a dual luciferase reporter assay, RNA pull-down and RNA immunoprecipitation experiments were used to explore the interaction between circAGFG1 and miR-203. Our results revealed that expression levels of circAGFG1 and miR-203 are upregulated in non-small-cell lung cancer tissues. CircAGFG1 enhances NSCLC cell proliferation, invasion, migration and epithelial-mesenchymal transition in vitro. Mechanistic analyses indicated that circAGFG1 acts as a sponge for miR-203 to repress the effect of miR-203 on its target, ZNF281. In conclusion, our study suggests that circAGFG1 promotes NSCLC growth and metastasis though a circAGFG1/miR-203/ZNF281 axis and may represent a novel therapeutic target.

摘要

环状 RNA circAGFG1 被报道在三阴性乳腺癌的进展中起着重要作用。然而,circAGFG1 在非小细胞肺癌(NSCLC)中的作用机制尚不清楚。在本研究中,通过实时 PCR 检测了 20 对 NSCLC 组织和相邻组织中 circAGFG1 的表达。接下来,在体外进行了带有 circAGFG1 的功能实验,以评估 circAGFG1 在肿瘤转移和生长中的作用。同时,进行了双荧光素酶报告基因检测、RNA 下拉和 RNA 免疫沉淀实验,以探索 circAGFG1 与 miR-203 之间的相互作用。我们的结果表明,circAGFG1 和 miR-203 的表达水平在非小细胞肺癌组织中上调。CircAGFG1 增强了 NSCLC 细胞的体外增殖、侵袭、迁移和上皮间质转化。机制分析表明,circAGFG1 作为 miR-203 的海绵,抑制了 miR-203 对其靶基因 ZNF281 的作用。总之,我们的研究表明,circAGFG1 通过 circAGFG1/miR-203/ZNF281 轴促进 NSCLC 的生长和转移,可能代表一种新的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/068d/6669801/8d464f0a3627/TCA-10-1692-g001.jpg

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