MicroRNA-107 inhibits tumor growth and metastasis by targeting the BDNF-mediated PI3K/AKT pathway in human non-small lung cancer.
MicroRNA-107 inhibits tumor growth and metastasis by targeting the BDNF-mediated PI3K/AKT pathway in human non-small lung cancer.
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MicroRNA-107通过靶向BDNF介导的PI3K/AKT通路抑制人非小细胞肺癌的肿瘤生长和转移
DOI：
10.3892/ijo.2016.3628
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发表时间：
2016-10
影响因子：
5.2
通讯作者：
Lv X
中科院分区：
文献类型：
--
作者：
Xia H;Li Y;Lv X
在非小细胞肺癌中发现了microRNA-107(miR-107)的异常表达。然而，其在非小细胞肺癌进展和转移中的作用和分子机制尚不清楚。因此，本研究的目的是阐明miR-107在NSCLC进展和转移中的潜在作用及其分子机制。实时定量聚合酶链式反应显示miR-107在非小细胞肺癌组织和细胞系中的表达水平显著降低。肿瘤组织中miR-107的低水平与TNM分期和淋巴结转移有关。功能分析显示，在体外，miR-107过表达抑制了A549细胞的增殖、迁移和侵袭，在体内抑制了NSCLC肿瘤的生长。进一步的机制分析表明，脑源性神经营养因子(BDNF)是非小细胞肺癌细胞miR-107的靶基因。此外，BDNF在NSCLC组织中的表达上调，且与miR-107呈负相关。强制过表达BDNF可有效逆转miR-107对NSCLC增殖、迁移和侵袭的抑制作用。MIR-107过表达或下调BDNF均可抑制PI3K/AKT信号通路的激活。综上所述，我们的发现首次证明miR-107可以通过靶向BDNF和间接调节PI3K/AKT信号通路来抑制NSCLC的转移，这可能为以miR-107和BDNF为靶点的人NSCLC提供潜在的治疗策略。
Abnormal expression of microRNA-107 (miR-107) was found in non-small cell lung cancer (NSCLC). However, little is known about its role and molecular mechanism in NSCLC progression and metastasis. Therefore, the aims of this study were to clarify the potential role of miR-107 and molecular mechanism in NSCLC progression and metastasis. Quantitative real-time polymerase chain reaction assay showed that miR-107 expression levels were significantly decreased in NSCLC tissue and cell lines. Low miR-107 levels in tumor tissue correlated with advanced TNM stage and lymph node metastasis. Function assays showed that overexpression of miR-107 suppressed cell proliferation, migration and invasion in A549 cells in vitro, and inhibited NSCLC tumor growth in vivo. Further mechanism assays suggested the brain-derived neurotrophic factor (BDNF) was identified as a target gene of miR-107 in NSCLC cells. In addition, BDNF expression was upregulated, and inversely correlated with miR-107 in NSCLC tissues. Enforced overexpression of BDNF effectively reversed the tumor suppressive functions of miR-107 on NSCLC proliferation, migration and invasion. miR-107 overexpression or downregulation of BDNF was able to inhibit activation of PI3K/AKT signaling pathway. Taken together, our findings present the first evidence that miR-107 could suppress NSCLC metastasis by targeting BDNF and indirectly regulating PI3K/AKT signaling pathway, which might lead to a potential therapeutic strategy focusing on miR-107 and BDNF for human NSCLC.
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DOI：
10.1097/igc.0000000000000456
发表时间：
2015-07-01
影响因子：
4.8
作者：
Yan, Hongliang;Wu, Weiguang;Wang, Zheng
通讯作者：
Wang, Zheng
影响因子：
--
作者：
De la Cruz-Morcillo MA;Berger J;Sánchez-Prieto R;Saada S;Naves T;Guillaudeau A;Perraud A;Sindou P;Lacroix A;Descazeaud A;Lalloué F;Jauberteau MO
通讯作者：
Jauberteau MO
影响因子：
3.9
作者：
Huang, Ssu-Ming;Lin, Chingju;Yeh, Wei-Lan
通讯作者：
Yeh, Wei-Lan
影响因子：
4.6
作者：
Zhang, Li;Ma, Ping;Song, Min
通讯作者：
Song, Min
DOI：
10.1016/j.lungcan.2014.07.014
发表时间：
2014-10
期刊：
Lung cancer (Amsterdam, Netherlands)
影响因子：
--
作者：
Schabath MB;Nguyen A;Wilson P;Sommerer KR;Thompson ZJ;Chiappori AA
通讯作者：
Chiappori AA