e20015 Background: Small cell lung cancer (SCLC) is regarded as the most devastative type of human lung malignancies, mostly due to their rapid and disseminated growth pattern. However, the molecular factors that drive rapid progression of SCLC remain unclear. Friend leukemia virus integration 1( FLI1),an Ets transcription factor family member, was identified as a proto-oncogene in some tumors via regulation of different target genes. In this study, we explored the potential role of FLI1 in SCLC. Methods: FLI1 protein expression was evaluated by immunohistochemistry in 67 primary SCLC, 20 non-small cell lung cancer (NSCLC) and 20 normal lung specimens. Correlation between FLI1 expression and clinical characteristics was evaluated with the logistic regression. Cell proliferation, cell cycle, apoptosis, colony formation assays in vitro and tumorigenesis assay in vivo were used to explore the function of FLI1 in SCLC cells. Use the miR-17-92 promoter/luciferase reporter assay to identify the regulation of FLI1 on miR-17-92 cluster promoter. Results: Immunohistochemical staining data showed that FLI1 was significantly upregulated in SCLC tissues compared to that in NSCLC and normal lung tissues ( p< 0.01). The expression score of FLI1 oncoprotein was associated with the extensive stage of SCLC and the overexpressed Ki67. Knockdown of FLI1 promoted apoptosis and induced repression of cell proliferation, tumor colony formation and in vivo tumorigenicity in highly aggressive SCLC cell lines. Importantly, we discovered that FLI1 promoted tumorigenesis by activating the miR-17-92 cluster family transcritption. Conclusions: This study uncovers that FLI1 is an important driving factor that promotes tumor growth in SCLC through the miR-17-92 pathway, and may serve as an attractive target for therapeutic intervention of SCLC.
Friend leukemia virus integration 1 promotes tumorigenesis of small cell lung cancer cells by activating the miR-17-92 pathway
