The regulation of hypoxia-induced NFIL3 in lung adenocarcinoma progression

• Main Authors: Ming-Hsuan Tsai, 蔡明軒
• Other Authors: Teh-Ying Chou
• Format: Others
• Language: zh-TW
• Published: 2018
• Online Access: http://ndltd.ncl.edu.tw/handle/np6syz

碩士 === 國立陽明大學 === 生化暨分子生物研究所 === 106 === Hypoxia is one of the most common features of tumor microenvironment. Tissue hypoxia has been reported to be associated with poor patient prognosis in many cancers including lung cancer. Our previous results indicated that lung cancer patients with high NFIL3 expression in the tumor have poor overall survival. Hypoxia upregulated NFIL3 mRNA and protein expression in many lung adenocarcinoma cell lines. NFIL3 protein expression was not induced by hypoxia when transcription was inhibited by actinomycin D treatment. Luciferase reporter assays showed that NFIL3 promoter activity was increased under hypoxia. These results suggested that the hypoxia-induced increase of NFIL3 expression was through transcriptional regulation. Overexpression of HIF1α or HIF2α could mimic the effect of hypoxia on NFIL3 expression. When HIF1α but not HIF2α was depleted, NFIL3 mRNA and protein levels still elevated under hypoxia, suggesting that there may exist functional redundancy between HIF1α and HIF2α in regulating NFIL3 expression. Results of the clonogenic assay showed similar fold change of colony number between cells with or without NFIL3 knockdown no matter under normoxia or hypoxia, demonstrating that NFIL3 knockdown could reduce cell growth under normoxia but have less effect on cell growth under hypoxia. Finally, we found a statistically significant positive correlation between NFIL3 and HIF1α expression (r = 0.228, p < 0.003) in lung cancer tissue microarrays.