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

肺癌中 microRNA 的药物敏感性预测和治疗策略的制定

• 批准号: 21591008
• 负责人: SEIKE Masahiro
• 金额: $ 3万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21591008/
• 关键词: マイクロRNA; 肺癌; 薬剤感受性

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.

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。

项目成果

肺癌の発生と薬剤感受性に関与するmiR-21の意義

miR-21参与肺癌发生和药物敏感性的意义

• 发表时间: 2011
• 作者: Yamaguchi E;et al.;清家正博
• 通讯作者: 清家正博

Gene expression profiles in lung cancer cells cooperated with drug sensitivity to PKC inhibitor enzastaurin

肺癌细胞中的基因表达谱与 PKC 抑制剂 enzastaurin 的药物敏感性相配合

• 发表时间: 2010
• 作者: 清家正博;他
• 通讯作者: 他

肺癌のEGFR-TKI感受性に関するmicroRNA研究

肺癌EGFR-TKI敏感性的MicroRNA研究

• 发表时间: 2010
• 作者: 清家正博;岡野哲也;添野千絵;峯岸裕司;野呂林太郎;吉村明修;弦間昭彦;末岡栄三朗;清家正博
• 通讯作者: 清家正博

非喫煙者肺癌およびEGFR-TKI感受性に関与するmiR-21の役割

miR-21 在非吸烟肺癌和 EGFR-TKI 敏感性中的作用

• 发表时间: 2009
• 作者: 清家正博;岡野哲也;吉村明修;弦間昭彦
• 通讯作者: 弦間昭彦

MicroRNA expression profiles modulate the drug sensitivity of lung cancer cells

MicroRNA表达谱调节肺癌细胞的药物敏感性

• 发表时间: 2009
• 作者: Seike M;Noro R;Soeno C;Shimokawa T;Miyanaga A;Yoshimura A and Gemma A
• 通讯作者: Yoshimura A and Gemma A