BPTF promotes glioma development through USP34-mediated de-ubiquitination of FOXC1.

Abstract

Glioma is the most prevalent malignant tumor of the brain, and the study of the molecular mechanisms associated with its development has important clinical significance. Our previous study found that BPTF promotes the malignant phenotype of glioma and is significantly associated with poor prognosis; the downstream regulatory mechanisms are explored in this study. Western blot and immunohistochemical staining were used to detect protein expression in cells or tissues. BPTF knockdown as well as FOXC1-overexpressing lentiviruses were used in combination for the construction of the U251 cell model, leading to functional rescue experiments. CCK8 assay, flow cytometry, scratch assay, and Transwell assay were used to detect cell proliferation, apoptosis, and migration, respectively. Finally, immunoprecipitation assays, combined with western blot (WB), were used to detect the interaction between proteins as well as the level of ubiquitination modification. The obtained results suggested that BPTF knockdown may inhibit the malignant behavior of glioma cells by downregulating FOXC1 expression. Moreover, FOXC1 expression was significantly higher in glioma tissues than in normal brain tissues and was significantly associated with higher tumor stage and worse patient prognosis. Finally, the mechanism of FOXC1 regulation by BPTF was found to result from the affected protein stability of FOXC1 through USP34-mediated de-ubiquitylation. In conclusion, the BPTF/FOXC1 axis was identified as a key promotor in glioma development and may be a potential target in the inhibition of glioma development.