Elevation in the Expression of circ_0079586 Predicts Poor Prognosis and Accelerates Progression in Glioma via Interactions with the miR-183-5p/MDM4 Signaling Pathway

• Main Authors: Chen J, Liu T, Wang H, Wang Z, Lv Y, Zhao Y, Yang N, Yuan X
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-06-01
• Series: OncoTargets and Therapy
• Subjects: glioma; circular rna; circ_0079586; mir-183-5p; mdm4 protein.
• Online Access: https://www.dovepress.com/elevation-in-the-expression-of-circ0079586-predicts-poor-prognosis-and-peer-reviewed-article-OTT

Jingyu Chen,1 Tianyi Liu,2 Hui Wang,3 Zhipeng Wang,1 Yanju Lv,4 Yuying Zhao,1 Ning Yang,1 Xueli Yuan1 1Department of Oncology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province 150001, People’s Republic of China; 2Department of Pathology, The Second Hospital of Harbin Medical University, Harbin, Heilongjiang Province 150086, People’s Republic of China; 3Department of Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong Province 250117, People’s Republic of China; 4Department of Oncology, The Second Hospital of Harbin Medical University, Harbin, Heilongjiang Province 150086, People’s Republic of ChinaCorrespondence: Xueli YuanDepartment of Oncology, The Fourth Affiliated Hospital of Harbin Medical University, No. 37, YiYuan Street, NanGang District, Harbin 150001, People’s Republic of ChinaTel [phone]Email [e-mail]: Glioma (GM) usually presents with an aggressive behavior and has a poor survival outcome. The abnormal expression of circular RNAs (circRNAs) has already been detected in GM, and circ_0079586 was found to have an increased expression in GM tumors.Patients and Methods: We assessed the differences in the expression of circ_0079586 in GM tissues (N=60) and cell lines (N=5) using qRT-PCR. The clinical value of circ_0079586 was measured by Fisher’s exact test and Kaplan–Meier and Cox regression analyses. Circ_0079586 siRNA and vector were transfected into LN229 and U251 cells, respectively, and the transfection was verified by qRT-PCR. Cell growth was evaluated by cell counting kit-8 (CCK-8). Cell apoptosis was measured using flow cytometric assay. Cell metastatic properties were measured by wound scratch and transwell experiments. Subcellular fractionation was used to identify the location of circ_0079586. Dual-luciferase reporter test was utilized to confirm the interaction between miR-183-5p and circ_0079586/MDM4 3ʹ-UTR.Results: The expression of circ_0079586 was elevated in GM samples and cells and correlated with the clinical severity and unfavorable prognosis of the patients. The elevated expression of circ_0079586 led to an increase in cell growth, migration and invasion but inhibited apoptosis in U251 cells, whereas its down-regulation reversed these effects in the LN229 cells. Mechanistically, we found circ_0079586 to be primarily located in the cytoplasm of GM cells. Furthermore, circ_0079586 could act as a sponge for miR-183-5p and elevate MDM4 expression at the posttranscriptional level.Conclusion: In summary, circ_0079586 was found to be up-regulated in GM that increased the proliferation, migration and invasion in GM cells via interaction with the miR-183-5p/MDM4 axis. We anticipate that our study would provide newer insights into the mechanism and treatment of GM.Keywords: glioma, circular RNA, circ_0079586, miR-183-5p, MDM4 protein