Prediction of drug sensitivity and development of a therapeutic strategy by microRNAs in lung cancer

本研究旨在寻找与肺癌药物敏感性相关的microRNAs（miRNAs），为肺癌的治疗提供新的思路。首先，我们使用Taqman MicroRNA Arrays分析了30种肺癌细胞系的miRNA表达谱。4种miRNAs（miR-21、miR-31、miR-193 b和miR-365）是与肺癌对9种抗癌药物敏感性相关的常见miRNAs。接下来，我们分析了恩扎鲁肽在22个肺癌细胞系中的抗肿瘤作用。为了鉴定与这种敏感性相关的miRNA，我们对同一组细胞系进行了miRNA表达谱研究。我们发现miR-21通过JAK/STAT信号通路影响肺癌中对enzaelatin的反应。最后，我们通过实时荧光定量PCR分析了miR-23 a/24/27 a在10个非小细胞癌细胞系中的表达。评估这些miRNA的表达与上皮-间质转化（EMT）之间的相关性。我们发现miR-23 a通过靶向E-cadherin调节TGF-β诱导的EMT，并促进肺癌细胞对EGFR-TKI的耐药。这些与药物敏感性相关的miRNAs可能成为肺癌治疗的新靶点。

We tried to identify microRNAs(miRNAs) associated with drug sensitivity of lung cancer and establish a new therapeutic strategy in lung cancer. First, we analyzed miRNA expression profiles of 30 lung cancer cell lines using Taqman MicroRNA Arrays. Four miRNAs(miR-21, miR-31, miR-193b and miR-365) were common miRNAs correlated with the sensitivity of lung cancer to nine anticancer drugs. Next, we analyzed the antitumor effects of enzastaurin in 22 lung cancer cell lines. To identify miRNA associated with this sensitivity, we conducted a miRNA expression profiling study on the same set of cell lines. We found that miR-21 affects the response to enzastaurin through the JAK/STAT signaling pathway in lung cancer. Finally, we analyzed miR-23a/24/27a expression in 10 non-small cell cancer cell lines by real-time PCR analysis. Correlation between expression of these miRNAs and epithelial-mesenchymal transition(EMT) was evaluated. We found that miR-23a regulated TGF-β-induced EMT by targeting E-cadherin and contributed to EGFR-TKI resistance of lung cancer cells. These miRNAs associated with drug sensitivity may be useful as new therapeutic targets in lung cancer.