Highlights High level of TFRC promotes the glioma development. Hsa-miR-144-3p inhibitor glioma growth by targeting TFRC. LncRNA RP1-86C11.7 exacerbates glioma progression through sponging to hsa-miR-144-3p, resulting in TFRC upregulation.

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.

Transforming growth factor β‐induced factor homeobox 1 (TGIF1) reportedly promotes the pathological processes of various malignant tumors. However, few studies have investigated the role of TGIF1 in gliomas. We aimed to explore the relationship between TGIF1 expression and the clinical characteristics of patients with glioma, including their overall survival. A total of thousands transcriptome datapoints were downloaded from public databases to determine the correlations between TGIF1 and various clinicopathological features using the Wilcoxon or Kruskal–Wallis tests. The Kaplan–Meier and Cox statistical methods were used to explore the prognostic significance of TGIF1. Gene set enrichment analysis (GSEA) was used to indirectly identify the pathological mechanisms modulated by TGIF1, and compounds that inhibit its expression were determined using a connectivity map (CMap). TGIF1 was significantly overexpressed in gliomas and was correlated with unfavorable prognostic factors and shorter overall survival. Cox analysis confirmed that TGIF1 expression was a significant predictor of poor prognosis in patients with glioma. GSEA revealed that the signaling pathways associated with TGIF1 expression in glioma included extracellular matrix receptor‐ and cell cycle‐modulating proteins. CMap analysis showed that the small molecules scriptaid, torasemide, dexpropranolol, ipratropium bromide, and harmine were potential negative regulators of TGIF1. Finally, in vitro experiments demonstrated that knockdown of TGIF1 significantly inhibited the proliferation and invasion of glioma cell. Taken together, our study, which is the first to comprehensively analyze TGIF1 in gliomas, revealed it to be a novel oncogene in terms of its association with this disease. As such, TGIF1 may be a potential therapeutic target for individualized treatment of patients with glioma.