Identification of microRNA profiles in docetaxel-resistant human non-small cell lung carcinoma cells (SPC-A1).
Identification of microRNA profiles in docetaxel-resistant human non-small cell lung carcinoma cells (SPC-A1).
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DOI：
10.1111/j.1582-4934.2009.00964.x
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发表时间：
2010-01
影响因子：
5.3
通讯作者：
Long-Bang C
中科院分区：
文献类型：
--
作者：
Rui W;Bing F;Hai-Zhu S;Wei D;Long-Bang C
多西他赛已作为一线化疗药物用于晚期非小细胞肺癌（NSCLC）的治疗，但耐药性的存在阻碍了多西他赛的进一步广泛有效应用。microRNAs（miRNAs）是近年来发现的重要的转录后调节因子，参与多种生物学过程。本研究的目的是确定参与NSCLC多西他赛耐药发展的microRNA表达谱。本研究采用微阵列芯片技术检测人非小细胞肺癌耐药细胞株（SPC-A1/docetaxel）中miRNA的表达谱。实时荧光定量RT-PCR（qRT-PCR）检测细胞中miRNAs的表达变化（与对照SPC-A1细胞相比>2倍）。此外，通过各种靶点预测工具分析了由选定的miRNA调控的潜在靶基因。SPC-A1/多西他赛细胞与对照SPC-A1细胞共表达52条miRNAs，差异有统计学意义（P < 0.01）。6个miRNAs（miR-192、200 b、194、424、98和212）的表达水平变化超过2倍，这通过qRT-PCR验证。3种miRNAs（miR-200 b、194和212）在SPC-A1/多西他赛细胞中的表达显著下调，而另外3种miRNAs（miR-192、424和98）在SPC-A1/多西他赛细胞中的表达显著上调（P <0. 01）。根据不同的功能将6个miRNAs控制的潜在靶基因分为4组：凋亡和增殖（71个基因）、细胞周期（68个基因）、DNA损伤（26个基因）和DNA修复（59个基因）。通过qRT-PCR和Western blot进一步证实了SPC-A1/多西他赛和SPC-A1细胞中少数靶基因的表达。总之，鉴定耐紫杉醇的NSCLC细胞中的microRNA表达谱可以更好地了解药物敏感性或耐药性的机制，这将有助于开发化疗无效NSCLC患者的靶向治疗新策略。
Docetaxel has been used as first-line chemotherapy in advanced non-small cell lung carcinoma (NSCLC), but further extensive and effective application is prevented by drug resistance. MicroRNAs (miRNAs) have recently been identified as important posttranscriptional regulators, which are involved in various biological processes. The aim of this study was to identify microRNA expression profiles involved in the development of docetaxel resistance in NSCLC. Here, microarray chip technology was employed to identify miRNA expression profiles in docetaxel-resistant human NSCLC cell line (SPC-A1/docetaxel). Then, the changes of miRNAs expression (>2-fold compared with control SPC-A1 cell line) were testified by quantitative real-time RT-PCR (qRT-PCR) assay. Furthermore, the potential target genes regulated by selected miRNAs were analysed by various target prediction tools. The expression of a total of 52 miRNAs showed significant difference between SPC-A1/docetaxel cells and control SPC-A1 cells (P < 0.01). Six miRNAs (miR-192, 200b, 194, 424, 98 and 212) exhibited more than 2-fold changes in their expression levels, which were validated by qRT-PCR. The expression of three miRNAs (miR-200b, 194 and 212) was significantly down-regulated in SPC-A1/docetaxel cells, while the expression of other three miRNAs (miR-192, 424 and 98) was significantly up-regulated in SPC-A1/docetaxel cells (P < 0.01). Potential target genes controlled by six selected miRNAs were divided into four groups according to various functions: apoptosis and proliferation (71 genes), cell cycle (68 genes), DNA damage (26 genes) and DNA repair (59 genes). The expression of a few target genes in SPC-A1/docetaxel and SPC-A1 cells were further confirmed by qRT-PCR and Western blot. Taken together, the identification of microRNA expression profiles in docetaxel-resistant NSCLC cells could provide a better understanding of mechanisms involved in drug sensitivity or resistance, which would be helpful to develop novel strategies for targeted therapies in chemorefractive NSCLC patients.
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