Biol-06. Novel Oncogenic Role for Nfia in Glioma
Year: 2017
Type: conference-abstract
Abstract: The Nuclear Factor I-A (NFIA) transcription factor is a glioma tumor promoter. However, the mechanism by which NFIA regulates glioma cell survival and drug resistance is still unknown. Here we report that the NFIA pro-survival effect is mediated via an NFIA-NFκB p65 feedforward loop. We examined effects of gain- and loss-of-function manipulations of NFIA and NFκB p65 on cell growth, colony formation, apoptosis and sensitivity to chemotherapy in patient-derived glioma stem cell (GSC). Ectopic NFIA inhibited apoptosis by activation of NFkB p65 and its downstream anti-apoptotic factors. Induction of NFκB by NFIA was required for apoptosis evasion, and inhibition of NFκB effectively reversed the NFIA anti-apoptotic effect. Furthermore, overexpression of NFIA promoted colony formation of non-transformed glial cells. Conversely, NFIA knockdown decreased expression of NFκB and its downstream anti-apoptotic genes and increased baseline apoptosis. Using a genome-wide approach, we demonstrated that NFIA directly regulated NFκB transcription. Interestingly, we also found that NFκB activated the NFIA transcription and that knockdown of NFIA was sufficient to attenuate the NFκB pro-survival effect, suggesting a reciprocal regulation between NFIA and NFκB in governing GBM cell growth and survival. Supporting this, NFIA and NFκB expression levels were highly correlated in human GBMs and GSC. Collectively, these data define a novel NFIA-NFκB feedforward regulation that promotes GBM malignant behavior.
Source: Neuro-Oncology
Authors: Edlira Hoxha, Kloetgen Andreas, Hae-Ri Song
Institution: New York University
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2618411755