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Circ-EGFR Functions as an Inhibitory Factor in the Malignant Progression of Glioma by Regulating the miR-183-5p/TUSC2 Axis
Cellular and Molecular Neurobiology ( IF 3.6 ) Pub Date : 2021-05-15 , DOI: 10.1007/s10571-021-01099-y
Qingdong Guo 1 , Jun Guo 2 , Wei Liu 1 , Shijie Hu 1 , Xuean Hu 1 , Qianliang Wang 3 , Xiaofan Jiang 1
Affiliation  

Circular RNAs (circRNAs) have pivotal functions in regulating diverse biological processes of human tumors, including glioma. Herein, a novel circRNA epidermal growth factor receptor (circ-EGFR, hsa_circ_0080223) was researched in glioma. The molecular expression levels were analyzed via quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK-8) and colony formation assays were conducted to assess cell proliferation. Apoptosis was analyzed using flow cytometry. Cell migration and invasion were examined via transwell assay. Interaction relations between targets were verified using dual-luciferase reporter assay. Tumor Suppressor Candidate 2 (TUSC2) protein expression was examined by Western blot. In vivo experiment was performed by establishing xenograft model in mice. The qRT-PCR showed the downregulation of circ-EGFR and TUSC2 but the upregulation of microRNA-183-5p (miR-183-5p) in glioma samples. In vitro assays revealed that circ-EGFR overexpression induced the repression of cell proliferation, migration, and invasion but the promotion of apoptosis. Circ-EGFR was identified as a sponge of miR-183-5p and circ-EGFR-mediated glioma progression inhibition was abolished by miR-183-5p downregulation. Additionally, miR-183-5p targeted TUSC2 and miR-183-5p inhibitor impeded the development of glioma by upregulating the expression of TUSC2. Furthermore, circ-EGFR could regulate the TUSC2 level by sponging miR-183-5p. Glioma growth in vivo was also reduced by circ-EGFR via targeting the miR-183-5p/TUSC2 axis. Altogether, our results suggested that circ-EGFR inhibited the malignant progression of glioma by regulating the levels of miR-183-5p and TUSC2. Circ-EGFR may be a useful therapeutic target to antagonize the glioma progression.



中文翻译:

Circ-EGFR 通过调节 miR-183-5p/TUSC2 轴作为胶质瘤恶性进展的抑制因子

环状 RNA (circRNA) 在调节人类肿瘤(包括神经胶质瘤)的多种生物学过程中具有关键作用。在此,研究了一种新型 circRNA 表皮生长因子受体(circ-EGFR,hsa_circ_0080223)在胶质瘤中的作用。通过定量实时聚合酶链反应(qRT-PCR)分析分子表达水平。进行细胞计数 Kit-8 (CCK-8) 和集落形成测定以评估细胞增殖。使用流式细胞术分析细胞凋亡。通过transwell测定检查细胞迁移和侵袭。使用双荧光素酶报告基因测定验证靶标之间的相互作用关系。通过蛋白质印迹检查肿瘤抑制候选物 2 (TUSC2) 蛋白表达。通过建立小鼠异种移植模型进行体内实验。qRT-PCR 显示胶质瘤样本中 circ-EGFR 和 TUSC2 下调,但 microRNA-183-5p (miR-183-5p) 上调。体外试验表明,circ-EGFR 过表达诱导细胞增殖、迁移和侵袭的抑制,但促进细胞凋亡。Circ-EGFR 被鉴定为 miR-183-5p 的海绵,并且 miR-183-5p 下调消除了 circ-EGFR 介导的神经胶质瘤进展抑制。此外,miR-183-5p 靶向 TUSC2 和 miR-183-5p 抑制剂通过上调 TUSC2 的表达来阻止胶质瘤的发展。此外,circ-EGFR 可以通过海绵化 miR-183-5p 调节 TUSC2 水平。circ-EGFR 通过靶向 miR-183-5p/TUSC2 轴也可以减少体内胶质瘤的生长。共,我们的研究结果表明,circ-EGFR 通过调节 miR-183-5p 和 TUSC2 的水平来抑制胶质瘤的恶性进展。Circ-EGFR 可能是对抗胶质瘤进展的有用治疗靶点。

更新日期:2021-05-15
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