The Expression and Oncogenic Role of NTSR2 in Human Glioblastoma

Abstract

Background/Aims: Neurotensin receptor 2 (NTSR2) plays critical pro-tumor roles in multiple human solid tumors. However, the expression characteristics, biological function and molecular mechanism of NTSR2 in glioblastoma (GBM) remain poorly elucidated. Methods: Bioinformatics analysis was used to analyze NTSR2 expression and its clinical prognostic significance in GBM. NTSR2 expression in glioma tissues was validated by immunohistochemistry, Western blot (WB) and RT-qPCR, while immunofluorescence staining detected its subcellular localization. In vitro functional assays were performed to evaluate the effects of NTSR2 on GBM cell proliferation, apoptosis, migration and invasion. The downstream molecules and AKT signaling pathway were verified via bioinformatics tools, WB and RT-qPCR. A mouse intracranial xenograft model with in vivo fluorescence imaging was established to validate the tumor-modulating role of NTSR2. Results: NTSR2 was significantly downregulated in glioma tissues and negatively correlated with pathological grade. Functional experiments confirmed that NTSR2 promotes proliferation, migration, invasion and inhibits apoptosis in GBM cells. Mechanistically, NTSR2 activates AKT signaling and modulates the expression of downstream effectors, including Cyclin B1/CDK4, ASCL1, POSTN, proBDNF and Caspase-3. In vivo imaging results further verified that NTSR2 knockdown markedly suppresses intracranial tumor growth. Conclusion: Despite decreased expression in GBM tissues, NTSR2 functions as an oncogenic driver to facilitate GBM malignant progression by activating the AKT signaling pathway and regulating downstream POSTN/proBDNF axes.