Repression of the expression of PPP3CC by ZEB1 confers activation of NF-κB and contributes to invasion and growth in glioma cells

Abstract

Background

Gliomas are highly malignant brain tumors. Aberrant activation of NF-κB plays a crucial role in tumor progression.

Method

ELISA assay was used to detect NF-κB activity in glimoas cells with different treatments. PPP3CC expression was evaluated by qRT-PCR and western blot assay. Kaplan–Meier analysis estimated the overall survival rates according to the protein level of PPP3CC. Transwell and MTS assay were performed to determine cell invasion and growth. Chromatin immunoprecipitation combined with luciferase reporter assays illustrated the transcriptional regulation of PPP3CC.

Results

We showed that PPP3CC decrease was responsible for constitutive activation of NF-κB in gliomas. Restored PPP3CC expression inhibited activation of NF-κB. PPP3CC was frequently decreased in gliomas and that repression of the expression of PPP3CC correlated glioma progression. The ectopic expression of PPP3CC inhibited the invasive potential of glioma cells, and inhibited glioma cells proliferation in vitro and growth in vivo. Additionally, the expression of Zinc finger E-box-binding homeobox 1(ZEB1) was increased in gliomas and was negatively correlated with clinical outcomes of glioma patients. ZEB1 inversely correlated with the expression of PPP3CC. ZEB1 was also confirmed to physically bind to the PPP3CC promoter. ZEB1 knockdown resulted in an increase in the expression of PPP3CC and elevation of PPP3CC promoter activity in glioma cells.

Conclusion

These findings indicated that the down-regulation of PPP3CC by ZEB1 resulted in activation of NF-κB is a critical oncogenic event in gliomas.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2nOmciI