Friend leukemia virus integration 1 promotes tumorigenesis of small cell lung cancer cells by activating the miR-17-92 pathway.
Friend leukemia virus integration 1 promotes tumorigenesis of small cell lung cancer cells by activating the miR-17-92 pathway.
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Friend白血病病毒整合1通过激活miR-17-92通路促进小细胞肺癌细胞肿瘤发生
DOI：
10.18632/oncotarget.16715
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发表时间：
2017-06-27
期刊：
影响因子：
--
通讯作者：
Cui J
中科院分区：
文献类型：
--
作者：
Li L;Song W;Yan X;Li A;Zhang X;Li W;Wen X;Zhou L;Yu D;Hu JF;Cui J
小细胞肺癌（small cell lung cancer，SCLC）是人类肺部恶性肿瘤中最具侵袭性的一种。快速和播散性生长模式仍然是SCLC患者临床预后不良的主要原因。然而，驱动SCLC快速进展的分子因素仍不清楚。Friend白血病病毒整合1（FLI 1）是Ets转录因子家族成员，以前曾报道过它是血液恶性肿瘤的主要驱动因素。在这项研究中，我们探讨了FLI 1在SCLC中的潜在作用。免疫组织化学染色发现FLI 1在SCLC组织中表达显著高于非小细胞肺癌（NSCLC）和正常肺组织（p < 0.01）。FLI 1癌蛋白表达评分与SCLC广泛分期及Ki 67过表达有关。用小干扰RNA（siRNA）或短发夹RNA（shRNA）敲低FLI 1可促进高度侵袭性SCLC细胞系的细胞凋亡并诱导细胞增殖、肿瘤集落形成和体内致瘤性的抑制。重要的是，我们发现FLI 1通过激活miR-17-92簇家族促进肿瘤发生。这项研究揭示了FLI 1作为一个重要的驱动因子，通过miR-17-92途径促进SCLC中的肿瘤生长。FLI 1可能作为一个有吸引力的小细胞肺癌治疗干预的目标。
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.
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影响因子：
11.2
作者：
Sohn EJ;Li H;Reidy K;Beers LF;Christensen BL;Lee SB
通讯作者：
Lee SB
影响因子：
11.4
作者：
Athanasiou, M;Mavrothalassitis, G;Blair, DG
通讯作者：
Blair, DG
影响因子：
--
作者：
Schwentner R;Herrero-Martin D;Kauer MO;Mutz CN;Katschnig AM;Sienski G;Alonso J;Aryee DN;Kovar H
通讯作者：
Kovar H
影响因子：
32.4
作者：
Hart, A;Melet, F;Bernstein, A
通讯作者：
Bernstein, A
影响因子：
64.8
作者：
George J;Lim JS;Jang SJ;Cun Y;Ozretić L;Kong G;Leenders F;Lu X;Fernández-Cuesta L;Bosco G;Müller C;Dahmen I;Jahchan NS;Park KS;Yang D;Karnezis AN;Vaka D;Torres A;Wang MS;Korbel JO;Menon R;Chun SM;Kim D;Wilkerson M;Hayes N;Engelmann D;Pützer B;Bos M;Michels S;Vlasic I;Seidel D;Pinther B;Schaub P;Becker C;Altmüller J;Yokota J;Kohno T;Iwakawa R;Tsuta K;Noguchi M;Muley T;Hoffmann H;Schnabel PA;Petersen I;Chen Y;Soltermann A;Tischler V;Choi CM;Kim YH;Massion PP;Zou Y;Jovanovic D;Kontic M;Wright GM;Russell PA;Solomon B;Koch I;Lindner M;Muscarella LA;la Torre A;Field JK;Jakopovic M;Knezevic J;Castaños-Vélez E;Roz L;Pastorino U;Brustugun OT;Lund-Iversen M;Thunnissen E;Köhler J;Schuler M;Botling J;Sandelin M;Sanchez-Cespedes M;Salvesen HB;Achter V;Lang U;Bogus M;Schneider PM;Zander T;Ansén S;Hallek M;Wolf J;Vingron M;Yatabe Y;Travis WD;Nürnberg P;Reinhardt C;Perner S;Heukamp L;Büttner R;Haas SA;Brambilla E;Peifer M;Sage J;Thomas RK
通讯作者：
Thomas RK