Abstract
High-grade glioma is highly invasive and malignant, resistant to combined therapies, and easy to relapse. A better understanding of circular RNA (circRNA) biological function in high-grade glioma might contribute to the therapeutic efficacy. Here, a circRNA merely upregulated in high-grade glioma, circGLIS3 (hsa_circ_0002874, originating from exon 2 of GLIS3), was validated by microarray and Real-time quantitative reverse transcription PCR (qRT-PCR). The role of circGLIS3 in glioma was assessed by functional experiments both in vitro and in vivo. Fluorescence in situ hybridization (FISH), RNA pull-down, RNA immunoprecipitation (RIP), and immunohistochemical staining were performed for mechanistic study. Cocultured brain endothelial cells with glioma explored the role of exosome-derived circGLIS3 in the glioma microenvironment. We found that upregulation of circGLIS3 promoted glioma cell migration and invasion and showed aggressive characteristics in tumor-bearing mice. Mechanistically, we found that circGLIS3 could promote the Ezrin T567 phosphorylation level. Moreover, circGLIS3 could be excreted by glioma through exosomes and induced endothelial cell angiogenesis. Our findings indicate that circGLIS3 is upregulated in high-grade glioma and contributes to the invasion and angiogenesis of glioma via modulating Ezrin T567 phosphorylation.
Highlights
Gliomas account for 25.1% of all primary brain and other central nervous system tumors according to CBTRUS (Central Brain Tumor Registry of the United States); approximately 70% of gliomas are high-grade gliomas (HGG, WHO grade III, and WHO grade IV gliomas) (Ostrom et al, 2020)
We proved that circGLIS3 can promote glioma invasion both in vitro and in vivo
Plasmid and control vector-transfected U251 cell lysates were incubated with biotin-labeled circGLIS3 probe (5 TGGTGTGGGTTATAAGCCTTTCCCAGGATTTG-3 -Biotin, Genepharm, Shanghai, China)
Summary
Gliomas account for 25.1% of all primary brain and other central nervous system tumors according to CBTRUS (Central Brain Tumor Registry of the United States); approximately 70% of gliomas are high-grade gliomas (HGG, WHO grade III, and WHO grade IV gliomas) (Ostrom et al, 2020). HGG are characterized by wide invasion; they can invade through vascular and brain parenchyma, which shelters them from surgery and radiotherapy and causes tumor recurrence in a short time (Cuddapah et al, 2014). HGG have abundant and aberrant vasculature; they advance in tumor progress through multiple angiogenesis mechanisms (Kane, 2019). Comprehensive treatment of surgery combined with chemoradiotherapy provides a benefit for patients with HGG, it remains largely refractory to treatment due to the high invasiveness and angiogenesis. Despite that developing treatments on reducing glioma progress such as anti-vascularization drugs are under investigation (Kim et al, 2018), the prognosis of HGG is still badly poor. It is necessary to explore the underlying mechanisms of glioma etiology for advancing the development of new effective therapy
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
