肺癌中RHOA和NKIRAS1基因的上调与其甲基化缺失以及调控性miRNA基因的甲基化有关。

Upregulation of RHOA and NKIRAS1 genes in lung tumors is associated with loss of their methylation as well as with methylation of regulatory miRNA genes.

作者信息

Braga E A, Loginov V I, Pronina I V, Khodyrev D S, Rykov S V, Burdennyy A M, Friedman M V, Kazubskaya T P, Kubatiev A A, Kushlinskii N E

机构信息

Institute of General Pathology and Pathophysiology, Moscow, 125315, Russia.

出版信息

Biochemistry (Mosc). 2015 Apr;80(4):483-94. doi: 10.1134/S0006297915040124.

DOI:10.1134/S0006297915040124

PMID:25869366

Abstract

Methylation of CpG-islands in promoter regions as well as interaction of miRNAs with messenger RNAs of target genes are related to multilayer mechanisms regulating gene expression. The goal of this study was to assess a possibility for miRNA gene methylation to influence indirectly activation of their target genes in lung tumors. By using a unified collection of samples of non-small cell lung cancer, it was demonstrated that elevated levels of mRNA for RHOA and NKIRAS1 genes were significantly (Spearman rank correlation, P < 10(-11)) associated both with loss of methylation in their CpG-islands and methylation in a number of miRNA genes, which, according to the miRWalk database, were predicted to possess regulatory functions. Novel potential regulatory miRNAs for RHOA (miR-9-1/-3, -34b/c, -129-2, -125b-1, -375, -1258) and NKIRAS1 (miR-34b/c, -129-2, -125b-1, -193a, -124a-1/-2/-3, -212, -132) genes in lung cancer were identified.

摘要

启动子区域CpG岛的甲基化以及微小RNA（miRNA）与靶基因信使核糖核酸（mRNA）的相互作用与调节基因表达的多层机制相关。本研究的目的是评估miRNA基因甲基化间接影响其在肺肿瘤中靶基因激活的可能性。通过使用非小细胞肺癌样本的统一收集，结果表明，RHOA和NKIRAS1基因的mRNA水平升高与它们CpG岛的甲基化缺失以及一些miRNA基因的甲基化显著相关（Spearman等级相关性，P < 10(-11)），根据miRWalk数据库预测，这些miRNA基因具有调控功能。确定了肺癌中RHOA（miR-9-1/-3、-34b/c、-129-2、-125b-1、-375、-1258）和NKIRAS1（miR-34b/c、-129-2、-125b-1、-193a、-124a-1/-2/-3、-212、-132）基因的新型潜在调控miRNA。