Nuclear factor I A promotes temozolomide resistance in glioblastoma via activation of nuclear factor κB pathway

Publication date: Available online 12 October 2019Source: Life SciencesAuthor(s): Xiao Yu, Maode Wang, Jie Zuo, Alafate Wahafu, Ping Mao, Ruichun Li, Wei Wu, Wanfu Xie, Jia WangAbstractAimsTo investigate the underlying mechanism by which glioblastoma (GBM) cells gain temozolomide (TMZ) resistance and to clarify novel therapeutic targets and new prognostic biomarkers for GBM.Main methodsA genome-wide hierarchical bi-clustering based on previously published microarray databases identified Nuclear Factor I A (NFIA) as one of the most significantly upregulated genes correlated to TMZ resistance in GBM. Then, the potential biological functions of NFIA in oncogenesis and chemoresistance were clarified by qRT-PCR, Western blotting and in vivo xenograft models with artificially induced TMZ-resistant U87 cells. Additionally, immunohistochemistry (IHC) assays were performed to explore the clinical significance of NFIA in glioma patients. Last, luciferase reporter assay was performed to study the transcriptional regulation of NFIA on the nuclear factor κb (NF-kB) pathway.Key findingsNFIA was correlated with TMZ resistance in GBM. Clinically, elevated NFIA expression was significantly correlated with adverse outcomes of glioma patients, especially in GBM patients. Moreover, NFIA contributed to the acquired TMZ resistance of GBM cells, while suppression of NFIA via lentivirus reduced cell proliferation, tumorigenesis and resistance to TMZ of GBM. Additionally, NFIA promoted transcripti...
Source: Life Sciences - Category: Biology Source Type: research