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circ-PITX1 通过海绵吸附 miR-518a-5p 上调白细胞介素 17 受体 D 的表达,促进胶质瘤细胞的进展。

Elevation of circ-PITX1 upregulates interleukin 17 receptor D expression via sponging miR-518a-5p and facilitates cell progression in glioma.

机构信息

Department of Neurology, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, China.

Department of Neurosurgery, The First Hospital of Qiqihar, Qiqihar, China.

出版信息

J Cell Biochem. 2019 Oct;120(10):16495-16502. doi: 10.1002/jcb.28868. Epub 2019 May 8.

Abstract

Glioma (GM) is one of the major global health problems across the world. Circular RNAs (circRNAs) have been increasingly identified and characterized in almost every aspect of biology, especially in cancer biology. This study desires to investigate the mechanism of circ-PITX1 on regulating GM development. Quantitative reverse-transcription polymerase chain reaction was carried out to measure the expression of circ-PITX1, which was upregulated in matched cancerous tissues and adjacent noncancerous tissues from 52 patients and four cell lines of GM. Fisher's exact indicated the upregulation of circ-PITX1 was associated with patients' tumor size and World Health Organization grade. Gain and loss-of-function assays demonstrated that circ-PITX1 could facilitate the growth, migration, and invasion and inhibit cell apoptosis in GM cell lines. What's more, circ-PITX1 sponges miR-518a-5p to release its repression on 3'-untranslated region (3'UTR) of interleukin 17 receptor D (IL17RD) messenger RNA to exert its oncogenic functions in GM cells proved by dual-luciferase reporter and rescue assays. Taken together, circ-PITX1 may play a critical role in GM and may be used as a therapeutic target for GM.

摘要

神经胶质瘤(GM)是全球范围内的主要健康问题之一。环状 RNA(circRNA)在生物学的几乎各个方面都得到了越来越多的鉴定和描述,尤其是在癌症生物学中。本研究旨在探讨 circ-PITX1 调节 GM 发展的机制。采用定量逆转录聚合酶链反应测量了 52 名患者和 4 种 GM 细胞系中配对的癌组织和相邻非癌组织中 circ-PITX1 的表达,结果表明 circ-PITX1 的表达上调。Fisher 确切检验表明,circ-PITX1 的上调与患者的肿瘤大小和世界卫生组织分级有关。增益和功能丧失试验表明,circ-PITX1 可促进 GM 细胞系的生长、迁移和侵袭,并抑制细胞凋亡。更重要的是,circ-PITX1 可作为 miR-518a-5p 的海绵体,释放对白细胞介素 17 受体 D(IL17RD)信使 RNA 3'非翻译区(3'UTR)的抑制作用,从而通过双荧光素酶报告和挽救试验证明其在 GM 细胞中的致癌作用。综上所述,circ-PITX1 在 GM 中可能发挥重要作用,并可作为 GM 的治疗靶点。

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