miR-497和miR-34a在铂敏感和铂耐药卵巢上皮癌患者中的表达差异及机制研究  

Expression Difference and Its Mechanisms of miR-497 and miR-34a in Platinum-sensitive and Platinum-resistant Epithelial Ovarian Carcinoma Patients

作　　者：曹丽娟[1] 刘文博[1] CAO Lijuan;LIU Wenbo(Dept. of Gynaecology and Obstetrics,Chengde Municipal Central Hospital,Hebei Chengde 067000,China)

机构地区：[1]承德市中心医院妇产科,河北承德067000

出　　处：《中国药房》2017年第17期2308-2313,共6页China Pharmacy

摘　　要：目的:探讨微小核糖核酸miR-497和miR-34a在铂敏感和铂耐药卵巢上皮癌(EOC)患者中表达的差异及机制。方法:选取2008年1月-2012年1月于我院妇产科行卵巢癌分期手术或肿瘤细胞减灭术的EOC患者72例,术后均行以铂类药物为基础的规范化疗,并进行随访(时间为2008年7月-2016年7月)。根据患者对铂类药物的敏感性将其分为铂敏感组(42例)和铂耐药组(30例)。采用实时荧光定量聚合酶链反应法检测两组患者肿瘤组织中miR-497和miR-34a的表达水平,并考察其与患者总生存时间的相关性;采用巢式降落式甲基化特异性聚合酶链反应法检测患者miR-497和miR-34a启动子区DNA甲基化水平,采用蛋白印迹法考察组蛋白H3第9位赖氨酸残基二甲基化(H3K9me2)水平,采用染色质免疫共沉淀法检测miR-497和miR-34a启动子区H3K9me2水平。结果:铂敏感组患者miR-497和miR-34a的表达水平均显著高于铂耐药组,差异均有统计学意义(P<0.05);72例患者的总生存期为(45.7±17.5)个月,与其miR-497和miR-34a表达水平呈正相关(r2分别为0.2714、0.3782,P<0.01)。铂耐药组患者miR-497和miR34a启动子区DNA甲基化水平均显著高于铂敏感组,且其启动子区H3K9me2水平也显著高于铂敏感组,差异均有统计学意义(P<0.05或P<0.01);而铂耐药组患者H3K9me2水平虽略高于铂敏感组,但差异无统计学意义(P>0.05)。结论:EOC患者肿瘤组织中miR-497和miR-34a的表达水平与铂化疗的敏感性及患者的生存时间有关,启动子区DNA甲基化和组蛋白甲基化可能是其表达变化的机制之一。OBJECTIVE:To investigate the expression difference and its mechanism of miR-497and miR-34a in platinum-sensitiveand platinum-resistant epithelial ovarian carcinoma(EOC)patients.METHODS:A total of72EOC patients underwent ovariancancer staging surgery or cytoreductive surgery were selected from department of gynaecology and obstetriscs of our hospital duringJan.2008-Jan.2012.They received standardized platinum chemotherapy after surgery and were followed up(during Jul.2008-Jul.2016).According to the sensitivity to platinum,those patients were divided into platinum-sensitive group(42cases)andplatinum-resistant group(30cases).Real-time fluorescent quantitative PCR was adopted to detect the expression of miR-497andmiR-34a in tumor tissue,and the relationship of it with total survival period was investigated.The levels of DNA methylation ofmiR-497and miR-34a promoter region were determined by nest type land type methylation specific PCR.Western blot assay wasused to detect the H3K9dimethylation(H3K9me2)levels.The H3K9me2levels of miR-497and miR-34a promoter region were determinedby chromatin immunoprecipitation method.RESULTS:The expression levels of miR-497and miR-34a in platinum-sensitivegroup were significantly higher than platinum-resistant group,with statistical significance(P<0.05).Total survival period of72patients was(45.7±17.5)months,which was positively correlated with the expression levels of miR-497and miR-34a(r2were0.2714,0.3782,P<0.01).The DNA methylation of miR-497and miR-34a promoter region in platinum-resistant group was significantlyhigher than platinum-sensitive group,and H3K9me2level of promoter region was significantly higher than platinum-sensitivegroup,with statistical significance(P<0.05or P<0.01).H3K9me2levels of platinum-resistant group were slightly higherthan that of platinum-sensitive group,but there was no statistical significance(P>0.05).CONCLUSIONS:The expression ofmiR-497and miR-34a in tumor tissue of EOC patients are related to the sensitivity of platinum chemotherapy and the survival

关 键 词：微小核糖核酸 miR-497 MIR-34A 卵巢上皮癌 铂耐药 DNA甲基化 组蛋白甲基化 启动子区 

分 类 号：R737.31[医药卫生—肿瘤]