Axl-altered microRNAs regulate tumorigenicity and gefitinib resistance in lung cancer.
Axl-altered microRNAs regulate tumorigenicity and gefitinib resistance in lung cancer.
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Axl 改变的 microRNA 调节肺癌的致瘤性和吉非替尼耐药性。
DOI：
10.1038/cddis.2014.186
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发表时间：
2014-05-15
影响因子：
9
通讯作者：
中科院分区：
文献类型：
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作者：
Axl激酶参与非小细胞肺癌（NSCLC）对酪氨酸激酶抑制剂（TKI）吉非替尼（gefitinib）或厄洛替尼（erlotinib）的获得性耐药，但Axl导致TKI耐药的机制在很大程度上是未知的。microRNAs（miRNAs）抑制基因表达，并且它们在肿瘤发生中的关键作用已经被牵连。为了研究miRNA在Axl介导的获得性吉非替尼耐药中的作用，我们检测了吉非替尼耐药肺癌中Axl介导的miRNA变化。鉴定了一组Axl激酶改变的miRNA。在这项研究中，我们验证并报告miR-374 a和miR-548 b调控Axl在细胞周期阻滞，吉非替尼诱导的细胞凋亡，上皮间质转化，迁移和肿瘤发生的吉非替尼耐药肺癌细胞在体外和体内的作用，通过靶向Wnt 5a和CCNB 1基因，分别。具有临床意义的是，Axl和miR-374 a的高表达以及miR-548 b的低表达与术后不良无病生存相关。这些结果表明，特定的miRNAs的调控可能提供一个治疗靶点，以治疗或逆转吉非替尼耐药的NSCLC与Axl的高表达在未来。
The involvement of Axl kinase in non-small cell lung cancer's (NSCLC) acquired resistance to tyrosine kinase inhibitors (TKIs) gefitinib or erlotinib has been identified recently, but the mechanism by which Axl contributes to TKI resistance is largely unknown. MicroRNAs (miRNAs) repress gene expression and their critical role in tumorigenesis has been implicated. To investigate the role of miRNAs in the Axl-mediated acquired gefitinib resistance, we examined the Axl-mediated miRNA changes in gefitinib-resistant lung cancers. A panel of Axl kinase-altered miRNAs was identified. In this study, we validate and report that miR-374a and miR-548b modulated by Axl have essential roles in cell cycle arrest, gefitinib-induced apoptosis, epithelial-to-mesenchymal transition, migration and tumorigenesis of gefitinib-resistant lung cancer cells in vitro and in vivo by targeting Wnt5a and CCNB1 genes, respectively. Of clinical significance, high expression of Axl and miR-374a and low expression of miR-548b are associated with poor disease-free survival postoperatively. These findings indicate that the modulation of specific miRNAs may provide a therapeutic target to treat or reverse gefitinib resistance in NSCLC with high expression of Axl in the future.
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影响因子：
51.1
作者：
Zhou, Caicun;Wu, Yi-Long;You, Changxuan
通讯作者：
You, Changxuan
影响因子：
13.5
作者：
Xia, Hongping;Ooi, London Lucien P. J.;Hui, Kam M.
通讯作者：
Hui, Kam M.
DOI：
10.1073/pnas.0909333107
发表时间：
2010-01-19
影响因子：
11.1
作者：
Gjerdrum, Christine;Tiron, Crina;Lorens, James B.
通讯作者：
Lorens, James B.
影响因子：
--
作者：
Wang, Yong-Sheng;Wang, Yin-Hua;Zhou, Cai-Cun
通讯作者：
Zhou, Cai-Cun
影响因子：
158.5
作者：
Mok, Tony S.;Wu, Yi-Long;Fukuoka, Masahiro
通讯作者：
Fukuoka, Masahiro