B-Myb Is Up-Regulated and Promotes Cell Growth and Motility in Non-Small Cell Lung Cancer.
B-Myb Is Up-Regulated and Promotes Cell Growth and Motility in Non-Small Cell Lung Cancer.
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B-Myb 在非小细胞肺癌中上调并促进细胞生长和运动
DOI：
10.3390/ijms18060860
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发表时间：
2017-05-27
影响因子：
5.6
通讯作者：
Bu Y
中科院分区：
文献类型：
--
作者：
Jin Y;Zhu H;Cai W;Fan X;Wang Y;Niu Y;Song F;Bu Y
B-Myb是一种过度表达的转录因子，在几种类型的人类癌症中发挥致癌作用。然而，其在肺癌中的潜在意义仍然难以捉摸。在本研究中，我们首次研究了B-Myb的表达谱及其在肺癌中的功能影响。实时荧光定量PCR和免疫组化分析显示，B-Myb在非小细胞肺癌（NSCLC）中异常表达，且与NSCLC的病理分级和临床分期呈正相关。一项功能获得性研究显示，B-Myb的过表达显著增加肺癌细胞的生长、集落形成、迁移和侵袭。相反，一项功能丧失研究表明，B-Myb的敲低降低了细胞的生长、迁移和侵袭。在NSCLC异种移植裸鼠模型中，B-Myb过表达也促进了体内肿瘤生长。通过RNA测序（RNA-seq）分析的分子机制研究显示，B-Myb过表达引起多种下游基因（例如，COL 11 A1、COL 6A 1、FN 1、MMP 2、NID 1、FLT 4、INSR和CCNA 1）和多种关键途径（例如，细胞外信号调节激酶（ERK）和磷酸化蛋白激酶B（Akt）信号通路）参与细胞增殖、肿瘤发生和转移。总的来说，我们的研究结果表明B-Myb在NSCLC中的肿瘤促进作用，因此暗示其作为NSCLC诊断和/或治疗靶点的潜力。
B-Myb is a transcription factor that is overexpressed and plays an oncogenic role in several types of human cancers. However, its potential implication in lung cancer remains elusive. In the present study, we have for the first time investigated the expression profile of B-Myb and its functional impact in lung cancer. Expression analysis by quantificational real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry demonstrated that B-Myb expression is aberrantly overexpressed in non-small cell lung cancer (NSCLC), and positively correlated with pathologic grade and clinical stage of NSCLC. A gain-of-function study revealed that overexpression of B-Myb significantly increases lung cancer cell growth, colony formation, migration, and invasion. Conversely, a loss-of-function study showed that knockdown of B-Myb decreases cell growth, migration, and invasion. B-Myb overexpression also promoted tumor growth in vivo in a NSCLC xenograft nude mouse model. A molecular mechanistic study by RNA-sequencing (RNA-seq) analysis showed that B-Myb overexpression causes up-regulation of various downstream genes (e.g., COL11A1, COL6A1, FN1, MMP2, NID1, FLT4, INSR, and CCNA1) and activation of multiple critical pathways (e.g., extracellular signal-regulated kinases (ERK) and phosphorylated-protein kinase B (Akt) signaling pathways) involved in cell proliferation, tumorigenesis, and metastasis. Collectively, our results indicate a tumor-promoting role for B-Myb in NSCLC and thus imply its potential as a target for the diagnosis and/or treatment of NSCLC.