MicroRNA let-7c inhibits migration and invasion of human non-small cell lung cancer by targeting ITGB3 and MAP4K3
MicroRNA let-7c inhibits migration and invasion of human non-small cell lung cancer by targeting ITGB3 and MAP4K3
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MicroRNA let-7c通过靶向ITGB3和MAP4K3抑制人非小细胞肺癌的迁移和侵袭
DOI：
10.1016/j.canlet.2013.08.030
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发表时间：
2014-01-01
期刊：
影响因子：
9.7
通讯作者：
Yang, Yue
中科院分区：
文献类型：
--
作者：
Zhao, Bingtian;Han, Haibo;Yang, Yue
microrna在肿瘤发生和转移过程中发挥着重要的调控作用。据报道，let-7家族的不同成员在人类肺肿瘤中减少。然而，特异性let-7成员在非小细胞肺癌转移中的作用尚不明确。本研究在94例非小细胞肺癌中检测了let-7成员的表达，发现let-7c低水平表达与非小细胞肺癌患者的转移、静脉侵袭、TNM晚期和生存率差之间存在显著关联。一致地，let-7c在相对高度转移的细胞中的异位表达显著抑制了它们的迁移和侵袭。在转移潜力相对较低的细胞中，抑制let-7c可促进其运动和侵袭。然后我们分析了let-7c的潜在靶点，发现ITGB3和MAP4K3被let-7c直接抑制。在恢复ITGB3和MAP4K3的表达后，let-7c对肿瘤转移的影响部分逆转，更重要的是，在64个NSCLC组织中，ITGB3和MAP4K3的表达水平与let-7c呈负相关。总之，我们的研究结果表明let-7c通过降解ITGB3和MAP4K3，阻止NSCLC转移。2013爱思唯尔爱尔兰有限公司版权所有。
MicroRNAs play an important regulatory role in carcinogenesis and cancer metastasis. Different members of let-7 family have been reported to be decreased in human lung tumors. However, the effect of specific let-7 member on metastasis of NSCLC remains undefined. Our current study detected the expression of let-7 members in 94 cases of NSCLC and a significant association was noticed between low levels of let-7c expression and metastasis, venous invasion, advanced TNM stages and poor survival of NSCLC patients. Consistently, ectopic expression of let-7c in relatively highly metastatic cells remarkably suppressed their migration and invasion. Inhibition of let-7c in cells with relatively low metastatic potential promoted their motility and invasion. We then analyzed the potential targets of let-7c and found that ITGB3 and MAP4K3 were directly repressed by let-7c. Upon restoring the expression of ITGB3 and MAP4K3, the effects of let-7c on tumor metastasis were partially reversed, and more importantly, the expression levels of ITGB3 and MAP4K3 were inversely correlated with let-7c in 64 NSCLC tissues. Collectively, our results suggest that let-7c, by degrading ITGB3 and MAP4K3, prevents NSCLC metastasis. (C) 2013 Elsevier Ireland Ltd. All rights reserved.