PBX2-Mediated circTLK1 Activates JAK/STAT Signaling to Promote Gliomagenesis via miR-452-5p/SSR1 Axis

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.

Effects of Subtoxic Concentrations of Atrazine, Cypermethrin, and Vinclozolin on microRNA-Mediated PI3K/Akt/mTOR Signaling in SH-SY5Y Cells

“…Using TaqMan array Advanced miRNA (Thermo Fisher Scientific, Waltham, MA, USA), the differential expression of miRNAs in the SH-SY5Y cells from [1 μΜ]-exposed of EDCs and VH were profiled (data not shown). The candidate miRNAs were then selected owing to their reported or predicted role in neuronal proliferation and survival [ 30 , 31 , 32 , 33 , 34 ]. Among them, miR-18b-5p, miR-29b-3p, miR-146b-5p, miR-452-5p, and miR-653-5p were carefully chosen for qRT-PCR validation both in the undifferentiated and differentiated SH-SY5Y cells treated with ATZ, CYP, and VNZ [100 nM, 1 μΜ] for 48 h. The expression levels of miR-18b-5p, miR-29b-3p, miR-146b-5p, miR-452-5p and miR-653-5p were significantly downregulated by EDC treatment compared with the VH ( Table 1 ) in the differentiated SH-SY5Y cells.…”

Downregulation of hsa_circTLK1 represses non-small cell lung cancer progression by regulating miR-876-3p/SRSF7 axis

“…For instance, circTLK1 enhances renal cell carcinoma cell proliferation and metastasis via the regulation of miR-495-3p and CBL [ 17 ]. CircTLK1 mediates PBX2 activation of JAK/STAT signaling to promote glioma progression [ 18 ]. However, the mechanism of circTLK1 in NSCLC has not been reported.…”

A Novel CRISPR/Cas9 Screening Potential Index for Prognostic and Immunological Prediction in Low-Grade Glioma

“…Aberrant JAK-STAT signaling pathways in distinctive malignancies can cause misexpression of genes in additional carcinogenic pathways ( Chang and Lai, 2019 ). Accordingly, regulating the JAK-STAT pathway targets may improve LGG diagnosis and treatment ( Basheer et al, 2021 ; Li et al, 2021 ).…”