miRNA对肺癌化疗耐药调控研究进展

Research situation of miRNAs in regulating chemotherapy resistance of lung cancer

目的:总结miRNA对肺癌耐药调控的研究状况,并探讨其在预测肺癌对药物敏感性和耐药性中的作用。方法:应用PubMed及CNKI期刊全文数据库检索系统,以"miRNA和肺癌"等为关键词,检索2007-01-2013-01的相关文献,共检索到英文文献732篇,中文文献88篇。纳入标准:1)肺癌耐药相关机制;2)miRNA在肺癌耐药中的作用;3)miRNA预测肺癌细胞的药物敏感性。根据纳入标准,符合分析的文献33篇。结果:肺癌耐药机制包括药物吸收降低或排出增多、药物靶点改变、细胞修复功能增强及细胞凋亡的减弱等,涉及药物作用各个环节关键基因突变可能导致耐药发生。而miRNA为一类高度保守的非编码RNAs,通过对上述各环节关键基因表达的调控进而调节肺癌细胞对化疗药物的敏感性。在肺癌化疗耐药的患者中,肺癌细胞miRNA突变或表达异常,导致miRNA对靶基因如药物转运相关基因、细胞解毒功能相关基因、细胞损伤后自我修复能力相关基因、细胞凋亡相关基因及肿瘤上皮间质化相关基因等表达的异常调控,致使肺癌细胞化疗耐药产生。同时,根据这些miRNA表达情况可预测肺癌患者对药物的反应。结论:miRNA对肺癌细胞耐药调控发挥着重要作用,从而为肺癌化疗耐药预测提供了新的思路和手段。

OBJECTIVE：To summarize the research situation of miRNAs in the regulation of drug resistance of lung cancer and its role in the prediction of drug sensitivity and resistance. METHODS： To retrieve the articles from 2007 to 2013 by Pubmed and CNKI full-text database retrieval system with ＂lung cancer,miRNA＂ as key words and get 732 Eng- lish articles and 88 Chinese ones. Selection standard： 1）The mechanism of drug resistance of lung cancer 2）The role of miRNAs in predicting drug sensibility of lung cancer 3） The role of miRNA in drug resistance of lung cancer. According to the selection standard, 33 articles meet the requirement. RESULTS：Lung cancer resistance mechanisms include less drug absorption and more exclusion, changes in drug targets, stronger cell repairment and weaker apoptosis. Changes of any gene involving in drug effects lead to drug resistance. While miRNA,as a class of highly conserved non-coding RNAs,reg- ulated chemotherapeutic drug sensitivity of lung cancer cells through regulation of the expression of these key genes. In patients with chemotherapeutic drug resistance,mutation or abnormal expression of mieroRNAs in their lung cancer cells resulted in abnormal regulation of expression of the miRNA target genes such as drug transport related genes, cell detoxify related genes,cell sel^healing related genes, cell apoptosis related genes and tumor epithelial mesenchymal related gene, causing chemotherapeutic drug resistance of lung cancer cells. At the same time,expression level of these miRNAs can be used to predict sensitivity of patients with lung cancer to drugs. CONLUSION： MiRNA plays an important role in the regu- lation of lung cancer drug resistance,thus new ideas and methods are provided for the prediction in the resistance of lung cancer cells to chemotherapy.