Exosome-Mediated Transfer of circRNA-GLIS3 Enhances Temozolomide Resistance in Glioma Cells Through miR-548m/MED31 Axis

Abstract Background: TMZ resistance plays a critical role in the treatment of glioma, our research try to explore how circRNAs affect the chemosensitivity of glioma cells. Methods: In this study, we proceeded gene sequencing, and selected circRNAs specifically expressed in TMZ resistant cells and use them as target genes for subsequent studies; by knocking out the target gene we clarify its effect on TMZ resistant glioma proliferation, invasion, migration and cell apoptosis; through tumor-burdened animals we explore the effect of target gene in vivo environment. Results: In our research we revealed that circ-GLIS3 was significantly upregulated in TMZ resistant glioma cells. Functionally, knocking down circ-GLIS3 could inhibit proliferation, invasion, and migration abilities of TMZ resistant glioma cells; moreover, the downregulation of circ-GLIS3 could induce cell cycle arrest and apoptosis, while miR-548m inhibition and MED31 mRNA could reverse this progress. In vivo condition, the silencing of circ-GLIS3 could induce cell apoptosis and suppressed tumor growth. Mechanistically, circ-GLIS3 positively upregulated MED31 expression by sponging miR-548m. Conclusions: All these research findings demonstrate that circ-GLIS3 accelerates TMZ resistant glioma progression through miR-548m/MED31 axis.