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

发布时间：2018-11-28 20:51

【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(P0.05);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,P0.01)。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(P0.05或P0.01);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(P0.05)。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。
[Abstract]:Aim: to investigate the difference and mechanism of miR-497 and miR-34a expression in platinum-sensitive and platinum-resistant ovarian epithelial carcinoma (EOC). Methods: from January 2008 to January 2012, 72 patients with EOC underwent ovarian cancer staging or tumor cell reduction in our hospital from January 2008 to January 2012. All patients received standard chemotherapy based on platinum drugs after operation. And followed up (July 2008-July 2016). Patients were divided into platinum sensitive group (42 cases) and platinum resistant group (30 cases) according to their sensitivity to platinum. The expression levels of miR-497 and miR-34a in tumor tissues of the two groups were detected by real-time fluorescence quantitative polymerase chain reaction, and the correlation between the expression levels and the total survival time of the patients was investigated. Nested drop methylation specific polymerase chain reaction was used to detect the DNA methylation level in miR-497 and miR-34a promoter region, and the H3K9me2 level of lysine residue at site 9 of histone H3 was detected by Western blotting. The levels of H3K9me2 in miR-497 and miR-34a promoter were detected by chromatin immunoprecipitation. Results: the expression levels of miR-497 and miR-34a in platinum sensitive group were significantly higher than those in platinum resistant group (P0.05). The total survival time of 72 patients was (45.7 卤17.5) months, which was positively correlated with the expression of miR-497 and miR-34a (R2 = 0.2714, 0.3782, P0.01, respectively). The levels of DNA methylation in miR-497 and miR34a promoter in platinum resistant group were significantly higher than those in platinum sensitive group, and the H3K9me2 level in promoter was significantly higher than that in platinum sensitive group (P0.05 or P0.01). The level of H3K9me2 in platinum resistant group was slightly higher than that in platinum sensitive group, but the difference was not statistically significant (P0.05). Conclusion: the expression of miR-497 and miR-34a in tumor tissues of patients with EOC is related to the sensitivity of platinum chemotherapy and the survival time of patients. The promoter region DNA methylation and histone methylation may be one of the mechanisms of its expression change.
【作者单位】：承德市中心医院妇产科;
【分类号】：R737.31

【相似文献】