陈晓霞,李 剑.miR-34a调控肺癌EGFR耐药细胞株中MET信号通路探讨[J].中国肿瘤,2013,22(12):1020-1024.
miR-34a调控肺癌EGFR耐药细胞株中MET信号通路探讨
miR-34a Regulating MET Signaling Pathway in EGFR Resistant Lung Cancer Cell Lines
投稿时间:2013-06-17  
DOI:10.11735/j.issn.1004-0242.2013.12.A014
中文关键词:  肺癌  获得性耐药  miR-34a  MET
英文关键词:lung cancer  acquired resistance  miR-34a  MET
基金项目:浦东新区卫生局卫生科技项目(PW2011A-18)
作者单位
陈晓霞 上海市浦东新区浦南医院 
李 剑 上海市浦东新区浦南医院 
摘要点击次数: 1464
全文下载次数: 1192
中文摘要:
      摘 要:[目地] 研究肺癌耐药细胞株HCC827/GR中MET信号通路的调控,明确肺癌获得性耐药的分子机制。[方法] 使用HCC827细胞[epidermal growth factor receptor(EGFR)基因19外显子缺少的肺腺癌细胞株],在此细胞的基础上培养吉非替尼耐药细胞株。检测耐药细胞株中MET的表达,并使用RT-PCR的方法检测miR-34a的表达;使用TargetScan等生物信息学软件预测miR-34a的下游靶点,并在细胞内验证miR-34a是否可以调控MET的表达。[结果] 与HCC827细胞相比,HCC827/GR细胞株对吉非替尼明显耐药。在耐药HCC827/GR细胞株中,miR-34a低表达,MET高表达,而在HCC827细胞株中,miR-34a高表达,MET低表达。TargetScan生物信息学软件提示,MET是miR-34a的下游靶点之一。将携带荧光报告基团和MET 3′UTR的载体与miR-34a共转染入细胞后荧光度下降。[结论] miR-34a可能通过调控靶基因MET而参与EGFR-TKI的获得性耐药。
英文摘要:
      Abstract:[Purpose] To study the miR-34a regulating MET signaling pathway in EGFR resistant lung cancer cell lines,and to investigate the mechanisms of acquired resistance of lung cancer.[Methods] On the basis of HCC827 cells (epidermal growth factor receptor gene exon 19 deletions in lung adenocarcinoma cell lines),the gefitinib resistant cell lines were cultured. the expression of MET and miR-34a in the drug-resistant cell lines were detected by RT-PCR method. The downstream target of miR-34a were predicted by bioinformatics software such as TargetScan. Whether miR-34a could regulate the expression of MET in the intracellular was verified. [Results] HCC827/GR cell lines resistant to gefitinib approximately 100-fold compared with HCC827 cells. Low expression of miR-34a and high expression of MET in the resistant cell lines was found,while high expression of miR-34a and low expression of MET in the HCC827 cells. TargetScan bioinformatics software indicated MET is one of downstream target of miR-34a. The fluorescence was decreased when the vectors carried fluorescent reporter group and MET 3′UTR and miR-34 were co-transfected into cells.[Conclusion] MiR-34a involves in EGFR-TKI acquired resistance.It might regulate target genes MET.
在线阅读   查看全文  查看/发表评论  下载PDF阅读器