Year: 2025
Type: article
Abstract: The transcription factor ZBTB7B has been identified as a potential tumor suppressor through a CRISPR-Cas9-based functional screen of tumor-associated genes, as overexpression of ZBTB7B could significantly suppress tumor growth in the models of breast cancer brain metastasis, which prompted our further exploration of its inhibitory role in glioma. To elucidate the underlying mechanisms of this suppressive effect, lentiviral-mediated ZBTB7B overexpression was established in U118 and GL261 glioma cell lines, and systematic evaluation of tumorigenic capacity was performed through in vitro and xenograft assays. The results showed that ZBTB7B transcriptionally activated GPR17 expression, which suppressed protein kinase A phosphorylation, amplified mitochondrial reactive oxygen species generation, and triggered Caspase3-dependent apoptosis. Meanwhile, ZBTB7B upregulated CXCL10 secretion, which markedly enhanced CD4+ and CD8+ T cell accumulation. Clinical validation through multiplex immunofluorescence staining on a tissue microarray of 129 glioma samples revealed a progressive loss of ZBTB7B protein expression across WHO grades II to IV, inversely correlating with tumor malignancy. These findings demonstrate ZBTB7B as a dual-function tumor suppressor that concurrently induces intrinsic apoptosis and remodels the tumor immune microenvironment in glioma toward a 'hot' phenotype. Therefore, we propose ZBTB7B reactivation as a novel therapeutic strategy for glioma.
DOI: 10.1093/jmcb/mjaf043
Authors: Linmei Zhang, Haozhe Zhang, Chenxi Wang, Aoxin Jiang, Fei Zhao, Sifan Yang, Hong Lei, Xuelan Yu, Juan Ren, Chengfang Tang, Xiaofei Wang, Yanke Chen
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,900
OpenAlex ID: W4416719779