Circular RNA circPOSTN promotes neovascularization by regulating miR-219a-2-3p/STC1 axis and stimulating the secretion of VEGFA in glioblastoma

Abstract

AbstractGlioblastoma (GBM), the most malignant type of astrocytic tumor, is one of the deadliest cancers prevalent in adults. Along with tumor growth, patients with GBM generally suffer from extensive cerebral edema and apparent symptoms of intracranial hyper-pressure. Accumulating evidence has demonstrated that circRNA plays a critically important role in tumorigenesis and progression. However, the biological function and the underlying mechanism of circRNA in GBM remain elusive. In this study, by conducting gene expression detection based on 15 pairs of GBM clinical specimens and the normal adjunct tissues, we observed that circPOSTN showed abnormally higher expression in GBM. Both loss-of-function and gain-of-function biological experiments demonstrated that circPOSTN scheduled the proliferation, migration, and neovascularization abilities of GBM cells. Further, fluorescence in situ hybridization (FISH) assay, quantitative RT-PCR, and subcellular separation suggested that circPOSTN was predominately localized in the cytoplasm and may serve as a competing endogenous RNA (ceRNA). CircRNA-miRNA interaction prediction based on online analytical processing, AGO2-RIP assay, biotin labeled RNA pulldown assay, and dual-luciferase reporter assay revealed that circPOSTN sponged miR-219a-2-3p, limited its biological function, and ultimately upregulated their common downstream gene STC1. Finally, by carrying out in vitro and in vivo functional assays, we uncovered a new regulatory axis circPOSTN/miR-219a-2-3p/STC1 that promoted GBM neovascularization by increasing vascular endothelial growth factor A (VEGFA) secretion. Our study underscores the critical role of circPOSTN in GBM progression, providing a novel insight into GBM anti-tumor therapy.