Friend leukemia virus integration 1 promotes tumorigenesis of small cell lung cancer cells by activating the miR-17-92 pathway

// Lingyu Li 1 , Wei Song 1 , Xu Yan 1 , Ailing Li 3 , Xiaoying Zhang 1 , Wei Li 1 , Xue Wen 1 , Lei Zhou 1 , Dehai Yu 1 , Ji-Fan Hu 1, 2 and Jiuwei Cui 1 1 Cancer Center, The First Bethune Hospital of Jilin University, Changchun, China 2 Stanford University Medical School, Palo Alto Veterans Institute for Research, Palo Alto, CA, USA 3 Stanford University Medical School, Palo Alto Veterans Institute for Research, Palo Alto, CA, USA Correspondence to: Jiuwei Cui, email: cuijiuwei@jlu.edu.cn Ji-Fan Hu, email: jifan@stanford.edu Keywords: FLI1, lung cancer, miR-17-92, tumor, apoptosis Received: February 03, 2017 Accepted: March 20, 2017 Published: March 30, 2017 ABSTRACT Small cell lung cancer (SCLC) is regarded as the most devastative type of human lung malignancies. The rapid and disseminated growth pattern remains the primary cause of poor clinical prognosis in patients with SCLC. However, the molecular factors that drive rapid progression of SCLC remain unclear. Friend leukemia virus integration 1 ( FLI1 ), an Ets transcription factor family member, has been previously reported to act as a major driver of hematological malignancies. In this study, we explored the potential role of FLI1 in SCLC. Using immunohistochemical staining, we found that FLI1 was significantly upregulated in SCLC tissues, compared to that in non-small cell lung cancer (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 with small interfering RNA (siRNA) or short hairpin RNA (shRNA) 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. This study uncovers FLI1 as an important driving factor that promotes tumor growth in SCLC through the miR-17-92 pathway. FLI1 may serve as an attractive target for therapeutic intervention of SCLC.