Circular RNAs (circRNAs) are a type of endogenous non-coding RNAs， which have been considered to mediate diverse tumorigenesis including angiogenesis. The present study aims to elucidate the potential role and molecular mechanism of circ-SHKBP1 in regulating the angiogenesis of U87 glioma-exposed endothelial cells (GECs). The expression of circ-SHKBP1， but not linear SHKBP1， was significantly upregulated in GECs compared with astrocyte-exposed endothelial cells (AECs). circ-SHKBP1 knockdown inhibited the viability， migration， and tube formation of GECs dramatically. The expressions of miR-379/miR-544a were downregulated in GECs， and circ-SHKBP1 functionally targeted miR-544a/miR-379 in an RNA-induce... More
Circular RNAs (circRNAs) are a type of endogenous non-coding RNAs， which have been considered to mediate diverse tumorigenesis including angiogenesis. The present study aims to elucidate the potential role and molecular mechanism of circ-SHKBP1 in regulating the angiogenesis of U87 glioma-exposed endothelial cells (GECs). The expression of circ-SHKBP1， but not linear SHKBP1， was significantly upregulated in GECs compared with astrocyte-exposed endothelial cells (AECs). circ-SHKBP1 knockdown inhibited the viability， migration， and tube formation of GECs dramatically. The expressions of miR-379/miR-544a were downregulated in GECs， and circ-SHKBP1 functionally targeted miR-544a/miR-379 in an RNA-induced silencing complex (RISC) manner. Dual-luciferase reporter assay demonstrated that forkhead box P1/P2 (FOXP1/FOXP2) were targets of miR-544a/miR-379. The expressions of FOXP1/FOXP2 were upregulated in GECs， and silencing of FOXP1/FOXP2 inhibited the viability， migration， and tube formation of GECs. Meanwhile， FOXP1/FOXP2 promoted angiogenic factor with G patch and FHA domains 1 (AGGF1) expression at the transcriptional level. Furthermore， knockdown of AGGF1 suppressed the viability， migration， and tube formation of GECs via phosphatidylinositol 3-kinase (PI3K)/AKT and extracellular signal-regulated kinase (ERK)1/2 pathways. Taken together， the present study demonstrated that circ-SHKBP1 regulated the angiogenesis of GECs through miR-544a/FOXP1 and miR-379/FOXP2 pathways， and these findings might provide a potential target and effective strategy for combined therapy of gliomas.
