Purpose: 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