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环状 RNA (circRNA)-表皮生长因子受体(EGFR)通过调节 miR-183-5p/TUSC2 轴在胶质瘤恶性进展中起抑制因子作用。

Circ-EGFR Functions as an Inhibitory Factor in the Malignant Progression of Glioma by Regulating the miR-183-5p/TUSC2 Axis.

机构信息

Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, No.127, Changle West Road, Xincheng District, Xi'an, 710032, China.

Department of Radiology, School of Stomatology, Fourth Military Medical University, Xi'an, 710032, China.

出版信息

Cell Mol Neurobiol. 2022 Oct;42(7):2245-2256. doi: 10.1007/s10571-021-01099-y. Epub 2021 May 15.

Abstract

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.

摘要

环状 RNA(circRNA)在调控人类肿瘤的多种生物学过程中发挥着关键作用,包括神经胶质瘤。在此,研究了神经胶质瘤中的一种新型环状 RNA 表皮生长因子受体(circ-EGFR,hsa_circ_0080223)。通过实时定量聚合酶链反应(qRT-PCR)分析分子表达水平。使用细胞计数试剂盒-8(CCK-8)和集落形成实验评估细胞增殖。通过流式细胞术分析细胞凋亡。通过 Transwell 实验检测细胞迁移和侵袭。通过双荧光素酶报告基因实验验证靶标之间的相互作用关系。通过 Western blot 检测肿瘤抑制候选物 2(TUSC2)蛋白表达。通过建立异种移植模型在小鼠体内进行体内实验。qRT-PCR 显示神经胶质瘤样本中 circ-EGFR 和 TUSC2 的下调以及 microRNA-183-5p(miR-183-5p)的上调。体外实验表明,circ-EGFR 过表达诱导细胞增殖、迁移和侵袭抑制,但促进凋亡。circ-EGFR 被鉴定为 miR-183-5p 的海绵,并且 miR-183-5p 的下调消除了 circ-EGFR 介导的神经胶质瘤进展抑制。此外,miR-183-5p 靶向 TUSC2,并且 miR-183-5p 抑制剂通过上调 TUSC2 的表达阻碍了神经胶质瘤的发展。此外,circ-EGFR 可以通过海绵吸附 miR-183-5p 来调节 TUSC2 水平。circ-EGFR 还通过靶向 miR-183-5p/TUSC2 轴在体内抑制神经胶质瘤的生长。总之,我们的研究结果表明,circ-EGFR 通过调节 miR-183-5p 和 TUSC2 的水平抑制神经胶质瘤的恶性进展。circ-EGFR 可能是拮抗神经胶质瘤进展的有用治疗靶标。

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Roles of circular RNAs in regulating the development of glioma.环状RNA在调节胶质瘤发生发展中的作用。
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