Biochemistry (Moscow)

, Volume 80, Issue 4, pp 483–494 | Cite as

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

  • E. A. BragaEmail author
  • V. I. Loginov
  • I. V. Pronina
  • D. S. Khodyrev
  • S. V. Rykov
  • A. M. Burdennyy
  • M. V. Friedman
  • T. P. Kazubskaya
  • A. A. Kubatiev
  • N. E. Kushlinskii


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.

Key words

CpG-islands methylation miRNA target genes RHOA NKIRAS1 mRNA lung cancer 



allelic imbalance analysis




methylation-specific PCR


methylation-sensitive restriction enzyme analysis


non-small cell lung cancer


reverse-transcription polymerase chain reaction


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Copyright information

© Pleiades Publishing, Ltd. 2015

Authors and Affiliations

  • E. A. Braga
    • 1
    • 2
    Email author
  • V. I. Loginov
    • 1
    • 2
  • I. V. Pronina
    • 1
    • 2
  • D. S. Khodyrev
    • 3
  • S. V. Rykov
    • 4
  • A. M. Burdennyy
    • 1
  • M. V. Friedman
    • 5
  • T. P. Kazubskaya
    • 6
  • A. A. Kubatiev
    • 1
  • N. E. Kushlinskii
    • 6
  1. 1.Institute of General Pathology and PathophysiologyMoscowRussia
  2. 2.Research Center of Medical GeneticsRussian Academy of Medical SciencesMoscowRussia
  3. 3.Federal Research Clinical Center of Specialized Types of Medical Care and Medical TechnologiesFederal Medical and Biological Agency of RussiaMoscowRussia
  4. 4.State Research Institute of Genetics and Selection of Industrial MicroorganismsMoscowRussia
  5. 5.Vavilov Institute of General GeneticsRussian Academy of SciencesMoscowRussia
  6. 6.Blokhin Russian Cancer Research CenterMoscowRussia

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