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

Background: Temozolomide (TMZ) resistance plays a critical role in the treatment of glioma. This research tries to explore how circRNAs affect the chemosensitivity of glioma cells. Materials and Methods: In this study, the authors performed gene sequencing and selected circRNAs specifically expressed in TMZ-R cells and used them as target genes for subsequent studies. By knocking out the target gene, the authors clarify its effect on TMZ-R glioma proliferation, invasion, migration, and cell apoptosis; and through tumor-burdened animals, the authors explore the effect of the target gene in an in vivo environment. Results: In this research, the authors revealed that circ-GLIS3 was significantly upregulated in TMZ-R glioma cells. Functionally, knocking down circ-GLIS3 could inhibit proliferation, invasion, and migration abilities of TMZ-R glioma cells. Moreover, downregulation of circ-GLIS3 could induce cell cycle arrest and apoptosis, while miR-548m inhibition and MED31 mRNA could reverse this progress. In the in vivo condition, 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-R glioma progression through the miR-548m/MED31 axis.