lncRNA对乳腺癌化疗耐药作用研究进展

Progress of research on the mechanism of lncRNA in chemoresistance of breast cancer

目的长链非编码RNA(long non-coding RNA,LncRNA)参与机体多种反应,与乳腺癌细胞耐药性有密切关联。总结与乳腺癌细胞耐药有关的lncRNA及其作用机制,可为防治因耐药而引起的乳腺癌治疗失败,以及后期药物研制提供依据。方法应用PubMed和CNKI检索系统,以"乳腺癌、化疗、耐药、lncRNA"为关键词,检索2010-09-2017-05相关文献,共检出中文文献19条,英文文献29条。纳入标准:(1)乳腺癌化疗耐药;(2)研究结果中包含lncRNA与乳腺癌细胞耐药的关系。排除标准:(1)非乳腺癌化学治疗耐药;(2)非lncRNA相关的乳腺癌细胞耐药。根据纳入排除标准,符合分析的文献38篇。结果导致细胞耐药的原因有很多,包括ATP转运蛋白(ATP-binding cassette,ABC)表达增加;解毒系统有关基因表达增加或激活;药物作用靶点结构改变或受损靶点修复能力增强;肿瘤细胞存活相关应答因素的改变以及信号转导通路异常介导的耐药等。目前研究与乳腺癌化疗耐药相关的lncRNA有BCAR4、GAS5、HOTAIR、HOTAIR、HIFIA-AS2、AK124454和UCA1等。结论 lncRNA与乳腺癌耐药密切相关,但其作用机制仍须进一步研究以寻找有效的靶点,为靶向药物的研究提供有力支持。

OBJECTIVE lncRNAs（long non-coding RNAs）participate in multiple reactions,and plays an important role in the drug resistance in breast cancer.The purpose of this paper is to summarize the drug resistance mechanism of cancer cells and some lncRNAs associated with drug resistance in breast cancer cells that have been already reported and their mechanism.It can provide a basis for the prevention of the failure of the treatment of breast cancer caused by drug resistance and the development of drugs.METHODS With ＂lncRNAs,breast cancer,drug resistance,chemotherapy＂as keywords,the literature were searched in Pubmed and CINK database searching system between 2010-09 and 2017-05 and in total we found Chinese literature nineteen articles and English literature twenty-nine articles.The inclusion criteria：（1）chemotherapeutic resistance of breast cancer;（2）the aim of the article is to discuss the factors of the lncRNAs in the drug resistance in breast cancer cells.Exclusion criteria：drug resistance of breast cancer cells unrelated to lncRNA.Thirtyeight articles were enrolled in this paper according to the criteria.RESULTS The reasons for the drug resistance are various,including increasing expression of ABC（ATP-binding cassette）,increasing or activating the expression of the detoxication related genes,structural changes of the action target of the drugs or the enhancement of repair capacity of the damaged action target,changes of the cancer cells＇ survival relative factors,dysregulation of the signal transduction pathways.Currently,the lncRNAs associated with drug resistance in breast cancer cells include BCAR4,GAS5,HOTAIR,HOTAIR,HIFIA-AS2,AK124454,UCA1 and so on.CONCLUSION lncRNAs play important roles in the drug resistance in the breast cancer cells,but the mechanism of them need to be further studied to find effective action targets of chemotherapeutic drugs and furnish evidence for the Targeting Drug Development.