MicroRNA-708-5p acts as a therapeutic agent against metastatic lung cancer.
MicroRNA-708-5p acts as a therapeutic agent against metastatic lung cancer.
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MicroRNA-708-5p 作为转移性肺癌的治疗剂
DOI：
10.18632/oncotarget.6594
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发表时间：
2016-01-19
期刊：
影响因子：
--
通讯作者：
Luo Z
中科院分区：
文献类型：
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作者：
Wu X;Liu T;Fang O;Dong W;Zhang F;Leach L;Hu X;Luo Z
MicroRNAs （miRNAs）最近被认为是抗肿瘤转移治疗的靶点。开发有效的miRNA介导疗法对基础研究和临床实践都是一个挑战。在这里，我们提出了miR-708-5p介导的替代疗法治疗转移性肺癌的证据。与非转移性肺癌样本和癌细胞系相比，miR-708-5p的表达显著降低。miRNA在体外通过其直接靶点p21抑制细胞存活和转移，抑制肺癌细胞的PI3K/AKT通路和干细胞样特性。在非小细胞肺癌小鼠模型中，通过聚乙烯亚胺（PEI）介导的未经修饰的miRNA递送系统给药可以模拟肿瘤特异性凋亡。它还有效地保护了实验动物，使其不发生恶性转移，而没有引起任何观察到的毒性。这些发现有力地支持miR-708-5p作为一种新的有效的治疗非小细胞肺癌转移性恶性肿瘤的药物。
MicroRNAs (miRNAs) have recently been recognized as targets for anti-metastatic therapy against cancer malignancy. Development of effective miRNA mediated therapies remains a challenge to both basic research and clinical practice. Here we presented the evidence for a miR-708-5p mediated replacement therapy against metastatic lung cancer. Expression of miR-708-5p was substantially reduced in metastatic lung cancer samples and cancer cell lines when compared to non-metastatic counterparts. Expression of the miRNA suppressed cell survival and metastasis in vitro through its direct target p21, and inhibited the PI3K/AKT pathway and stem cell-like characteristics of lung cancer cells. Systemic administration of this miRNA in a mouse model of NSCLC using polyethylenimine (PEI)-mediated delivery of unmodified miRNA mimics induced tumor specific apoptosis. It also effectively protected the tested animals from developing metastatic malignancy without causing any observed toxicity. The findings strongly support miR-708-5p as a novel and effective therapeutic agent against metastatic malignancy of non-small cell lung cancer.