Background: Growing evidences indicate that circular RNAs (circRNAs) play an important role in the regulation of biological behavior of tumor. We aim to explore the role of circRNA in glioma and elucidate how circRNA acts. Methods: Real-time PCR was used to examine the expression of circPTN in glioma tissues and normal brain tissues (NBT). Assays of dual- luciferase reporter system, biotin label RNA pull-down and FISH were used to determine that circPTN could sponge miR-145-5p and miR-330-5p. Tumor sphere formation assay was performed to determine self- renewal of glioma stem cell (GSCs). Cell counting Kit-8 (CCK8), EdU assay and flow cytometry were used to investigate proliferation and cell cycle. Intracranial xenograft was established to determine how circPTN impacts in vivo. Tumor sphere formation assay was performed to determine self- renewal of glioma stem cell (GSCs). Results: We demonstrated circPTN was significantly higher expression in glioma tissues and glioma cell lines, compared with NBT and HEB (human astrocyte). In gain- and loss-of-function experiments, circPTN significantly promoted glioma growth in vitro and in vivo. Furthermore, we performed dual-luciferase reporter assays and RNA pull-down assays to verify that circPTN acts through sponging miR-145-5p and miR-330-5p. Increasing expression of circPTN rescued the inhibition of proliferation and downregulation of SOX9/ITGA5 in glioma cells by miR-145-5p/miR-330-5p. In addition, we found that circPTN promoted self-renewal and increased the expression of stemness markers (Nestin, CD133, SOX9, and SOX2) via sponging miR-145-5p. Moreover, this regulation was disappeared when circPTN binding sites in miR-145-5p were mutated. Conclusions: Our results suggest that circPTN is an oncogenic factor that acts by sponging miR-145-5p/miR-330-5p in glioma.

Glioblastoma multiforme (GBM) is the most aggressive and highly vascularized brain tumor with poor prognosis. Endothelial cell-dependent angiogenesis and tumor cell-dependent Vasculogenic mimicry (VM) synergistically contribute to glioma vascularization and progression. However, the mechanism underlying GBM vascularization remains unclear. In this study, GBM stem cells (GSCs) were divided into high and low β8 integrin (ITGB8) subpopulations. Co-culture assays followed by Cell Counting Kit-8 (CCK-8), migration, Matrigel tube formation, and sprouting assays were conducted to assess the proliferative, migratory and angiogenic capacity of GBM cells and human brain microvascular endothelial cells (hBMECs). An intracranial glioma model was constructed to assess the effect of ITGB8 on tumor vascularization in vivo. Our results indicated that ITGB8 expression was elevated in GSCs and positively associated with stem cell markers in glioma tissues, and could be induced by hypoxia and p38 activation. ITGB8 in GSCs inhibited the angiogenesis of hBMECs in vitro, while it promoted the ability of network formation and expression of VM-related proteins. The orthotopic GBM model showed that ITGB8 contributed to decreased angiogenesis, meanwhile enhanced invasiveness and VM formation. Mechanistic studies indicated that ITGB8-TGFβ1 axis modulates VM and epithelial-mesenchymal transition (EMT) process via Smad2/3-RhoA signaling. Together, our findings demonstrated a differential role for ITGB8 in the regulation of angiogenesis and VM formation in GBM, and suggest that pharmacological inhibition of ITGB8 may represent a promising therapeutic strategy for treatment of GBM.

Both vasculogenic mimicry (VM) and transforming growth factor-β (TGFβ) are positively correlated with malignancy in glioma. Accordingly, we supposed that TGFβ might be related with VM, and aimed to...