中文摘要：

目的：探讨酪氨酸激酶Axl调控的miRNA在非小细胞肺癌（ NSCLC）吉非替尼获得性耐药中的意义。方法：比较表皮生长因子受体（ EGFR）突变型NSCLC细胞株HCC827及其吉非替尼耐药株HCC827-Gef中Axl mRNA＆amp;nbsp；[实时荧光定量PCR（qRT-PCR）]和蛋白（Western blot）的表达，再利用微阵列分析筛选出20个差异表达miRNA，其中miR-374 a、miR-548 b敏感度最高；采用qRT-PCR检测Axl沉默对HCC827-Gef细胞miR-374 a、miR-548 b表达的影响；对不同Axl mRNA表达水平的NSCLC患者（共40例） miR-374 a、miR-548 b表达进行比较并进行Kaplan-Meier法生存分析。结果：HCC827-Gef 细胞中 Axl mRNA 及蛋白的表达均高于 HCC827细胞（ t ＝9．393，24．038；P＜0．001）。与转染空质粒的HCC827-Gef细胞比较，HCC827-Gef-esiAXL细胞中Axl mRNA、miR-374a表达下降，miR-548b表达则上调（t＝22．155，56．000，16．000；P＜0．001）。与Axl低表达的NSCLC患者比较，Axl mRNA高表达者癌组织中miR-374a表达升高，miR-548b表达降低（t＝5．231，2．473；P＜0．05），无病生存期缩短（χ2＝6．550，P＝0．011）。结论：Axl及其调控的miR-374a和miR-548b在NSCLC吉非替尼获得性耐药中起重要作用，可作为NSCLC预后标记或潜在的治疗靶点。

英文摘要：

Aim：To explore the significance of tyrosine kinase Axl-modulated miRNA in gefitinib-resistance for non-small cell lung cancer（NSCLC）.Methods：The expressions of Axl mRNA and protein in NSCLC cell lines HCC 827 with epidermal growth factor receptor mutation , and its gefitinib-resistant lung cancer cell HCC 827-Gef were detected by qRT-PCR and Western blot .Twenty differential expression miRNA were scaned by microarray analysis , and among which ,miR-374a and miR-548b were proved the most sensitive .qRT-PCR was used to detected the miR-374a and miR-548b expres-sions in HCC827-Gef silenced by esiAxl .The expressions of miR-374 a and miR-548 b in NSCLC patients with different Axl mRNA expression levels were compared , and survival analysis was performed by Kaplan-Meier method .Results：The ex-pressions of Axl mRNA and protein were significantly higher in HCC 827-Gef than those in HCC827（t=9.393,24.038;P〈0.001）.Down-regulated expression of miR-374a and up-regulated expression of miR-548b were detected in HCC827-Gef after Axl gene was knocked down （t=56.000,16.000;P〈0.001）.The patients with high Axl mRNA expression level had significantly higher expression of miR-374a and lower miR-548b（t=5.231,2.473;P〈0.05）,and shorter disease-free sur-vival time compared with patients with low Axl mRNA expression level （χ2 =6.550,P=0.011）.Conclusion：Axl and its modulated miR-374 a and miR-548 b may play important roles in gefitinib-resistance and may serve as a prognostic biomarker or potential therapeutic target for NSCLC .