LncRNA与非小细胞肺癌EGFR-TKIs耐药关系及机制研究进展  

Research progress on the relationship and mechanism of LncRNA in EGFR-TKIs resistance non-small cell lung cancer

作　　者：杨玲 马虎[1,2] 刘光峨 YANG Ling;MA Hu;LIUGuang-e(Department of Thoracic Oncology ,Affiliated Hospital of Zunyi Medical University ,Zunyi 563003 ,P. R. China;Biotherapy Talent Base of Guizhou Province ,Center for Translational Medicine ,Zunyi Medical University ,Zunyi 563003 ,P. R. China)

机构地区：[1]遵义医学院附属医院胸部肿瘤科,贵州遵义563003 [2]遵义医学院转化医学中心贵州省生物治疗人才基地,贵州遵义563003

出　　处：《中华肿瘤防治杂志》2018年第6期449-454,共6页Chinese Journal of Cancer Prevention and Treatment

基　　金：国家自然科学基金(81660512)

摘　　要：目的长链非编码RNA(long non-coding RNA,LncRNA)是一类转录长度>200个核苷酸的RNA,无蛋白质编码功能,广泛存在于各种生物中,其种类繁多,作用机制复杂。本文综述了LncRNA在非小细胞肺癌(non-small cell lung cancer,NSCLC)表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor tyrosine kinase inhibitor,EGFR-TKIs)耐药中的作用及机制。方法应用PubMed及中国知网等数据库,以"LncRNA、非小细胞肺癌、EGFRTKIs、耐药"等为关键词,检索2003-2018年的相关文献,共检索到文献166篇。纳入标准:(1)与NSCLC EGFR-TKIs相关的文献;(2)与NSCLC EGFR-TKIs耐药相关的文献;(3)与NSCLC EGFR-TKIs相关LncRNA的文献。根据纳入标准,最后分析51篇高度相关的文献。结果针对EGFR-TKIs耐药机制,除了常见的EGFR T790M突变外,多个研究表明LncRNA与EGFR-TKIs耐药的产生有密切的关系。异常表达的LncRNA可广泛调控基因的表达,通过参与X染色体沉默、基因组印记和转录激活等途径,调控细胞的增殖、分化及凋亡,参与肿瘤的发生和发展。在EGFR-TKIs敏感和耐药细胞中多种LncRNA表达不同,且通过不同的耐药机制参与EGFR-TKIs耐药,其中常见的有MALAT1、MIR31HG、UCA1、BC087858和GAS5等。结论深入研究LncRNA在NSCLC EGFR-TKIs耐药机制中所起的作用,有望为NSCLC EGFR-TKIs耐药患者找到新的靶点,进而延长患者的生存时间及提高患者的生活质量。OBJECTIVE Long non-coding RNA（LncRNA）is commonly defined as transcribed RNAs of more than200 nucleotides with no coding potential,which are involved in numerous important biological processes with a wide variety of types and a complex mechanism.This article reviews the role and mechanism of LncRNA in the resistance of epidermal growth factor receptor tyrosine kinase inhibitors（EGFR-TKIs）in non-small cell lung cancer.METHODS Using the keywords of＂LncRNA,non-small cell lung cancer,EGFR-TKIs,and drug resistance＂,we searched 166 papers for the related literatures in PubMed and CNKI from 2003 to 2018.Inclusion criterion：（1）Literatures related to EGFR-TKIs in non-small cell lung cancer;（2）Literatures related to EGFR-TKIs resistance in non-small cell lung cancer;（3）LncRNA related to EGFR-TKIs in non-small cell lung cancer.According to the inclusion criteria,we summarized 51 highly-related studies.RESULTS In addition to the common EGFR T790 M mutation of EGFR-TKIs resistance mechanisms,several studies have shown that LncRNA are closely related to the development of EGFR-TKIs resistance.Aberrant expressing of LncRNA can regulate the expression of genes widely,and participate in the occurrence and development of tumors by regulating X-chromosome silence,genomic imprinting,and transcriptional activation to regulate cell proliferation,differentiationand apoptosis.Multiple LncRNA are expressed differently in sensitive and resistant cells of EGFR-TKIs,and they participate in EGFR-TKIs resistance through different mechanisms.These LncRNA including MALAT1,MIR31 HG,UCA1,BC087858,GAS5 and so on.CONCLUSION Further research on the role and mechanism of LncRNA in non-small cell lung cancer with EGFR-TKIs resistance will find new targets for EGFR-TKIs resistant patients in non-small cell lung cancer,thereby prolonging the survival time and improving their quality of life.

关 键 词：非小细胞肺癌 长链非编码RNA 表皮生长因子受体酪氨酸激酶抑制剂 耐药 综述文献 

分 类 号：R734.2[医药卫生—肿瘤]