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Background  High-grade glioma has a poor prognosis, and GSCs can have pivotal roles in glioma pathology. This study investigated GSC exosome-containing circRNA mechanisms affecting the malignant progression of glioma.    Methods  In this study, we identified differentially expressed circRNAs and constructed a circRNA-miRNA-mRNA regulatory network through circRNA sequencing/bioinformatics analysis. Then, we identified circRNAs that were upregulated in GSC23 cells and employed them as downstream targets in subsequent investigations. Such investigations included downstream target knockout to assess any influence on A172 cell proliferation, invasion, migration and apoptosis. In addition, in vivo investigations using tumor-bearing animals evaluated the in vivo influences of the selected targets.    Results  This study identified circ-Serpine2/miR-124-3p/KIF20A as a regulatory pathway in glioma. Our in vitro analysis confirmed that circ-Serpine2 could upregulate KIF20A by sponging miR-124-3p, consequently promoting A172 cell proliferation, migration and invasion. Such a signaling channel could also inhibit glioma cell apoptosis. Additionally, our research indicated that circ-Serpine2 inhibited glioma apoptosis and promoted in vivo tumor progression.    Conclusion  Circ-Serpine2 exacerbated the malignant progression of glioma mediated by the miR-124-3p/KIF20A nexus, thus providing novel predictive/prognostic biomarkers and drug targets against glioma.

Bioinformatics analysis reveals a stem cell-expressed circ-Serpine2-mediated miRNA-mRNA regulatory subnetwork in the malignant progression of glioma