miR-27a regulates cisplatin resistance and metastasis by targeting RKIP in human lung adenocarcinoma cells.
miR-27a regulates cisplatin resistance and metastasis by targeting RKIP in human lung adenocarcinoma cells.
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DOI：
10.1186/1476-4598-13-193
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发表时间：
2014-08-16
期刊：
影响因子：
37.3
通讯作者：
Yu W
中科院分区：
文献类型：
--
作者：
Li J;Wang Y;Song Y;Fu Z;Yu W
MicroRNAs(MiRNAs)被认为是重要的转录后调节因子，参与细胞的各种生物学和病理过程，但其与肿瘤化疗耐药的关系尚未完全清楚。我们检测了miR-27A在两种肺腺癌细胞株A549和A549/CDDP中的表达，并通过功能获得和丧失研究探讨了miR-27A对癌细胞转移和化疗敏感性的影响。进一步探讨miR-27A水平与临床肺腺癌耐药的关系。与亲代A549细胞相比，MIR-27A在耐顺铂的肺腺癌A549/CDDP细胞中表达显著上调。MIR-27A在体外调节上皮-间充质转化(EMT)和顺铂耐药，并在体内调节肺腺癌细胞对顺铂的反应。进一步的研究证实Raf Kinase抑制蛋白(RKIP)是miR-27A的直接和功能靶点。小干扰RNA介导的RKIP基因敲除与异位表达miR-27A的作用相似，而过度表达RKIP则减弱了miR-27A在肺腺癌细胞中的功能。在接受以顺铂为基础的化疗的肺腺癌患者的肿瘤组织中也检测到miR-27A的表达增加，并被证明与RKIP的低表达、对顺铂的敏感性降低和预后不良有关。我们的结果提示miR-27A的上调可以抑制RKIP的表达，进而导致肺腺癌细胞对顺铂的化疗耐药。本文的在线版本(DOI：10.1186/1476-4598-13-193)包含补充材料，授权用户可以使用。
MicroRNAs (miRNAs) have been identified as important posttranscriptional regulators involved in various biological and pathological processes of cells, but their association with tumor chemoresistance has not been fully understood. We detected miR-27a expression in two lung adenocarcinoma cell lines, A549 and A549/CDDP, and then investigated the effects of miR-27a on the metastasis and the chemosensitivity of cancer cells, using both gain- and loss-of-function studies. The correlation between miR-27a level and chemoresistance was further investigated in clinical lung adenocarcinoma specimens. miR-27a was significantly up-regulated in cisplatin-resistant lung adenocarcinoma A549/CDDP cells compared with parental A549 cells. miR-27a regulates epithelial-mesenchymal transition (EMT) and cisplatin resistance in vitro and modulates response of lung adenocarcinoma cells to cisplatin in vivo. Further studies identified Raf Kinase Inhibitory Protein (RKIP) as a direct and functional target of miR-27a. Small interfering RNA-mediated RKIP knockdown revealed similar effects as that of ectopic miR-27a expression, while overexpression of RKIP attenuated the function of miR-27a in lung adenocarcinoma cells. Increased miR-27a expression was also detected in tumor tissues sampled from lung adenocarcinoma patients treated with cisplatin-based chemotherapy and was proved to be correlated with low expression of RKIP, decreased sensitivity to cisplatin, and poor prognosis. Our results suggest that up-regulation of miR-27a could suppress RKIP expression and in turn contribute to chemoresistance of lung adenocarcinoma cells to cisplatin. The online version of this article (doi:10.1186/1476-4598-13-193) contains supplementary material, which is available to authorized users.
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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