ZBTB7B Inhibits Glioma Tumorigenicity by Upregulating GPR17 and CXCL10

ABSTRACT: Background: We utilized a CRISPR-Cas9 screening library to examine the functions of tumor-related genes. Among these, we identified the transcription factor ZBTB7B, which overexpressed in breast cancer cells and significantly inhibited breast cancer growth in the brains of nude mice. Based on this finding, we hypothesized that ZBTB7B might exert similar effects on glioma, a possibility not yet explored in the literature. This study aims to evaluate the effects and mechanisms of ZBTB7B in glioma progression. Methods:The U118 and the GL261 cell line , both overexpressing ZBTB7B, were generated via lentiviral transduction. The impact of ZBTB7B on glioma growth was assessed using in vitro cell culture and in vivo intracranial inoculation. Downstream targets regulated by ZBTB7B were identified through transcriptome sequencing, PCR arrays, ELLA assays, and Western blotting. Cell apoptosis and the cell cycle were analyzed via flow cytometry. Multicolor immunofluorescence staining was performed to evaluate the expression and localization of ZBTB7B in human and mouse glioma tissues. Findings:Overexpression of ZBTB7B significantly inhibited glioma cell survival both in vitro and in vivo. Mechanistically, ZBTB7B upregulated the expression of GPR17, which suppressed PKA phosphorylation, promoted the generation of reactive oxygen species, and ultimately induced apoptosis. Additionally, ZBTB7B regulated the chemokine CXCL10, facilitating the recruitment of CD4+ and CD8+ T cells to the tumor periphery. Human glioma tissue microarray analysis revealed ZBTB7B expression was significantly reduced or absent in grade II to IV glioma samples. Interpretation:ZBTB7B exhibits significant tumor-suppressive effects and holds promise as a potential molecular target for glioma therapy.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE290306 | GEO | 2026/03/01

REPOSITORIES: GEO