PTBP1 knockdown promotes neural differentiation of glioblastoma cells through UNC5B receptor.

Cell reprogramming technology is utilized to prevent cancer progression by transforming cells into terminally differentiated, non-proliferating states. Polypyrimidine tract binding protein 1 (PTBP1) is an RNA binding protein required for the growth of neurons and may directly transform multiple normal human cells into functioning neurons and when expressed at low levels. As a result, we identified it as a key to inhibiting cancer cell proliferation by boosting glioblastoma cell neural differentiation. Immunocytofluorescence (ICF) targeting TUJ1, MAP2, KI67, and EdU were utilized to evaluate glioblastoma cell reprogramming under knockdown or other conditions. and other target genes were detected using Western blotting and qRT-PCR. Activating protein phosphatase 2A (PP2A) and RhoA were detected using specific kits. CCK8 assays were employed to detect cell viability. Bioluminescence, immunohistofluorescence (IHF), and Kaplan-Meier survival analyses were utilized to demonstrate the reprogramming efficiency of knockdown in U87 murine glioblastoma model. In this study, RNA-seq technology was used to examine the intrinsic pathway. The expression of TUJ1 and MAP2 neural markers, as well as the absence of KI67 and EdU proliferative markers in U251, U87, and KNS89 cells, indicated that glioblastoma cell reprogramming was successful. , U87 growth generated xenografts was substantially shrank due to knockdown induced neural differentiation, and these tumor-bearing mice had a prolonged survival time. Following RNA-seq, ten potential downstream genes were eliminated. Lentiviral interference and inhibitors blocking tests demonstrated that UNC5B receptor and its downstream signaling were essential in the neural differentiation process mediated by knockdown in glioblastoma cells. Our results indicate that knockdown promotes neural differentiation of glioblastoma cells via UNC5B receptor, consequently suppressing cancer cell proliferation and , providing a promising and feasible approach for glioblastoma treatment.