首页> 美国卫生研究院文献>Oncotarget >Methylation of miR-129-5p CpG island modulates multi-drug resistance in gastric cancer by targeting ABC transporters
【2h】

Methylation of miR-129-5p CpG island modulates multi-drug resistance in gastric cancer by targeting ABC transporters

机译:miR-129-5p CpG岛的甲基化通过靶向ABC转运蛋白来调节胃癌的多药耐药性

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。

摘要

Recent studies have reported that hyper-methylation in the promoter region of miRNAs could silence the expression of tumor suppressive miRNAs and might play significant roles in the process of tumor development. However, the potential mechanisms regarding how methylation of miRNA CpG Island could regulate cancer cell chemo-resistance have not yet been studied. Using microarray and BSP (Bisulfate Sequencing PCR) assays, we found that compared with the parent SGC7901/VCR cells, expression of miR-129-5p was restored in SGC7901/VCR gastric cancer multi-drug resistant cell line treated by de-methylation reagent (5-AZA-dC). Using gain or loss of function assays, we found the over-expressed miR-129-5p reduced the chemo-resistance of SGC7901/VCR and SGC7901/ADR cells, while down-regulation of miR-129-5p had an opposite effect. Furthermore, three members of multi-drug resistance (MDR) related ABC transporters (ABCB1, ABCC5 and ABCG1) were found to be direct targets of miR-129-5p using bioinformatics analysis and report gene assays. The present study indicated that hyper-methylation of miR-129-5p CpG island might play important roles in the development of gastric cancer chemo-resistance by targeting MDR related ABC transporters and might be used as a potential therapeutic target in preventing the chemo-resistance of gastric cancer.
机译:最近的研究报道,miRNAs启动子区域的高度甲基化可能使抑癌性miRNAs的表达沉默,并可能在肿瘤发展过程中发挥重要作用。然而,关于miRNA CpG岛的甲基化如何调节癌细胞化学耐药性的潜在机制尚未研究。使用微阵列和BSP(Bisulfate Sequencing PCR)分析,我们发现,与亲本SGC7901 / VCR细胞相比,用去甲基化试剂处理的SGC7901 / VCR胃癌多药耐药细胞系恢复了miR-129-5p的表达(5-AZA-dC)。使用功能获得或丧失的检测方法,我们发现过表达的miR-129-5p降低了SGC7901 / VCR和SGC7901 / ADR细胞的化学耐药性,而下调miR-129-5p则具有相反的作用。此外,使用生物信息学分析和报告基因分析,发现与多药抗性(MDR)相关的ABC转运蛋白的三个成员(ABCB1,ABCC5和ABCG1)是miR-129-5p的直接靶标。本研究表明,miR-129-5p CpG岛的超甲基化可能通过靶向与MDR相关的ABC转运蛋白而在胃癌化学耐药性的发展中发挥重要作用,并可能被用作预防化学耐药性的潜在治疗靶点胃癌。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号