Abstract
Glioma is considered one of the most lethal brain tumors, as the aggressive blood vessel formation leads to high morbidity and mortality rates. However, the mechanisms underlying the initiation and progression of glioma remain unclear. Here, we aimed to reveal the role of circTLK1 in glioma development. Our results revealed that circTLK1 is highly expressed in glioma tumor tissues and glioma cell lines. We then conducted a series of experiments that showed that circTLK1 was involved in the progression of gliomas. Mechanistically, investigation of the factors downstream of circTLK1 revealed that circTLK1 activated JAK/STAT signaling in glioma cells. Furthermore, AGO2-RIP, RNA-pull down, and luciferase reporter gene assays led to the identification of the novel circTLK1/miR-452-5p/SSR1 axis. Moreover, we investigated the upstream regulator of circTLK1 and found that circTLK1 expression in glioma cells could be regulated by the transcriptional factor PBX2. Taken together, our findings show that circTLK1 mediated by PBX2 activates JAK/STAT signaling to promote glioma progression through the miR-452-5p/SSR1 pathway. These results provide new insights into glioma diagnosis and therapy.
Highlights
Glioma is one of the most common subtypes of malignant brain cancers and accounts for approximately 27% of central nervous system tumors (Louis et al, 2016)
These findings suggests that circTLK1 may be involved in glioma development
We further explored whether circTLK1 mediates JAK/STAT signaling via the miR-452-5p/SSR1 axis
Summary
Glioma is one of the most common subtypes of malignant brain cancers and accounts for approximately 27% of central nervous system tumors (Louis et al, 2016). CircRNAs have been found to participate in the progression of multiple pathophysiological circTLK1 Contributes to Gliomagenesis processes, including cancers (Kristensen et al, 2018; Patop and Kadener, 2018; Di Agostino et al, 2020) They play critical roles in many biological processes of tumorigenesis, such as cell viability (Chen et al, 2017), invasion (Song et al, 2019), migration (Ren et al, 2019), and angiogenesis (Jia et al, 2016). Barbagallo et al (2018) demonstrated that circSMARCA5 affects the migration of glioblastoma multiforme cells by facilitating SRSF1/SRSF3/PTB axis activity These studies suggest an essential role of circRNA in glioma progression
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