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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

Authors
  • Braga, E. A.1, 2
  • Loginov, V. I.1, 2
  • Pronina, I. V.1, 2
  • Khodyrev, D. S.3
  • Rykov, S. V.4
  • Burdennyy, A. M.1
  • Friedman, M. V.5
  • Kazubskaya, T. P.6
  • Kubatiev, A. A.1
  • Kushlinskii, N. E.6
  • 1 Institute of General Pathology and Pathophysiology, Moscow, 125315, Russia , Moscow (Russia)
  • 2 Russian Academy of Medical Sciences, Research Center of Medical Genetics, Moscow, 115478, Russia , Moscow (Russia)
  • 3 Federal Medical and Biological Agency of Russia, Federal Research Clinical Center of Specialized Types of Medical Care and Medical Technologies, Moscow, 115682, Russia , Moscow (Russia)
  • 4 State Research Institute of Genetics and Selection of Industrial Microorganisms, Moscow, 117545, Russia , Moscow (Russia)
  • 5 Russian Academy of Sciences, Vavilov Institute of General Genetics, Moscow, 117971, Russia , Moscow (Russia)
  • 6 Blokhin Russian Cancer Research Center, Moscow, 115478, Russia , Moscow (Russia)
Type
Published Article
Journal
Biochemistry (Moscow)
Publisher
Pleiades Publishing
Publication Date
Apr 15, 2015
Volume
80
Issue
4
Pages
483–494
Identifiers
DOI: 10.1134/S0006297915040124
Source
Springer Nature
Keywords
License
Yellow

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.

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