miR-140-3p functions as a tumor suppressor in squamous cell lung cancer by regulating BRD9
miR-140-3p functions as a tumor suppressor in squamous cell lung cancer by regulating BRD9
复制标题
miR-140-3p 通过调节 BRD9 作为鳞状细胞肺癌的肿瘤抑制因子
DOI：
10.1016/j.canlet.2019.01.007
复制
发表时间：
2019-01-01
期刊：
影响因子：
9.7
通讯作者：
Hu, Rongkuan
中科院分区：
文献类型：
--
作者：
Huang, Haitao;Wang, Yuxuan;Hu, Rongkuan
鳞状细胞肺癌（SqCLC）是世界上最恶性的肺癌之一，缺乏诊断和治疗靶点的生物标志物。在这项研究中，我们观察到miR-140- 3 p在SqCLC细胞系和患者样本中均以低水平表达，而miR-140- 3 p的过表达显著降低了SqCLC细胞和患者来源的异种移植物（PDX）模型中的细胞增殖和侵袭。我们的进一步研究表明miR-140- 3 p通过下调癌基因BRD 9的表达而对SqCLC的肿瘤发生产生负面影响。BRD 9的抑制通过调节c-myc表达来抑制SqCLC肿瘤发生。同时，在临床样本中，BRD 9表达上调，并与miR-140- 3 p呈负相关;生存数据的荟萃分析表明，肿瘤中BRD 9水平高的SqCLC患者预后较差。总之，我们的研究表明miR-140- 3 p和BRD 9轴在鳞状细胞肺癌中的预后和治疗作用。
Squamous cell lung cancer (SqCLC) is among the most malignant lung cancers worldwide, lacking biomarkers for diagnostic and targets for treatment. In this study, we observed that miR-140-3p was expressed at low levels both in SqCLC cell lines and patient samples, while overexpression of miR-140-3p dramatically reduced the cell proliferation and invasion in SqCLC cells and Patient derived xenograft (PDX) models. Our further investigation indicated miR-140-3p negatively affected the tumorigenesis of SqCLC by down-regulating the expression of BRD9, an oncogene in SqCLC. Inhibition of BRD9 repressed SqCLC tumorigenesis by regulating c-myc expression. Meanwhile, BRD9 expression is up-regulated and negatively correlated with miR-140-3p in clinical samples; a meta-analysis of survival data indicates that SqCLC patients with high levels of BRD9 in their tumors have a worse prognosis. Collectively, our study suggests the prognostic and therapeutic roles of miR-140-3p and BRD9 axis in squamous cell lung cancer.