...
首页> 外文期刊>Epigenetics: official journal of the DNA Methylation Society >Epigenetically regulated MIR941 and MIR1247 target gastric cancer cell growth and migration
【24h】

Epigenetically regulated MIR941 and MIR1247 target gastric cancer cell growth and migration

机译:表观遗传调控的MIR941和MIR1247靶向胃癌细胞的生长和迁移

获取原文
获取原文并翻译 | 示例
           

摘要

Altered expression of microRNA (miRNA) can significantly contribute to cancer development and recent studies have shown that a number of miRNAs may be regulated by DNA methylation. Through a candidate gene approach, we identified MIR941 and MIR1247 to be transcriptionally silenced by DNA hypermethylation in several gastric cancer cell lines. We confirmed that these miRNAs are also densely methylated in primary gastric cancers but not in normal gastric tissues. In addition, we demonstrated that ectopic expression of these two miRNAs in AGS gastric cancer cells resulted in suppression of growth and migration. Furthermore, we tested genes predicted to be the targets of MIR941 and MIR1247 and identified 7 and 6 genes, whose expressions were significantly downregulated by transfection of MIR941 and MIR1247 mimics, respectively, in gastric cancer cell lines. Some of these genes are known to promote proliferation and invasion, phenotypes we observed upon ectopic expression of the two miRNAs. Thus, we examined these candidates more closely and found that downregulation of mRNA corresponded to a decrease in protein levels (observed by western blot). Our study provides unequivocal evidence that MIR941 and MIR1247 are transcriptionally regulated by DNA methylation in gastric cancer and that they have tumor suppressor properties through their inhibition of key cancer promoting genes in this context.
机译:microRNA(miRNA)的表达改变可能会大大促进癌症的发展,最近的研究表明,许多miRNA可能受到DNA甲基化的调节。通过候选基因方法,我们确定了MIR941和MIR1247在几种胃癌细胞系中被DNA超甲基化沉默。我们证实,这些miRNA在原发性胃癌中也被高密度甲基化,但在正常胃组织中没有。此外,我们证明了这两种miRNA在AGS胃癌细胞中的异位表达可抑制生长和迁移。此外,我们测试了预测为MIR941和MIR1247靶标的基因,并鉴定了7个和6个基因,其表达分别通过转染MIR941和MIR1247模拟物在胃癌细胞系中显着下调。已知其中一些基因可促进增殖和侵袭,这是我们在两个miRNA异位表达时观察到的表型。因此,我们更仔细地检查了这些候选物,发现mRNA的下调对应于蛋白质水平的下降(通过蛋白质印迹观察)。我们的研究提供了明确的证据,表明胃癌中MIR941和MIR1247受DNA甲基化的转录调控,并且在这种情况下它们通过抑制关键的促癌基因而具有抑癌特性。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

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