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

Circ-EGFR通过调节miR-183-5p/TUSC2轴在胶质瘤恶性进展中起抑制因子的作用

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作者:Qingdong Guo #, Jun Guo #, Wei Liu, Shijie Hu, Xuean Hu, Qianliang Wang, Xiaofan Jiang

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.

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