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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

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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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Abbreviations

AIA:

allelic imbalance analysis

miRNA:

microRNA

MSP:

methylation-specific PCR

MSRA:

methylation-sensitive restriction enzyme analysis

NSCLC:

non-small cell lung cancer

RT-PCR:

reverse-transcription polymerase chain reaction

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Author information

Authors and Affiliations

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

    E. A. Braga, V. I. Loginov, I. V. Pronina, A. M. Burdennyy & A. A. Kubatiev

  2. Research Center of Medical Genetics, Russian Academy of Medical Sciences, 115478, Moscow, Russia

    E. A. Braga, V. I. Loginov & I. V. Pronina

  3. Federal Research Clinical Center of Specialized Types of Medical Care and Medical Technologies, Federal Medical and Biological Agency of Russia, 115682, Moscow, Russia

    D. S. Khodyrev

  4. State Research Institute of Genetics and Selection of Industrial Microorganisms, 117545, Moscow, Russia

    S. V. Rykov

  5. Vavilov Institute of General Genetics, Russian Academy of Sciences, 117971, Moscow, Russia

    M. V. Friedman

  6. Blokhin Russian Cancer Research Center, 115478, Moscow, Russia

    T. P. Kazubskaya & N. E. Kushlinskii

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  1. E. A. Braga
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  2. V. I. Loginov
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  3. I. V. Pronina
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  4. D. S. Khodyrev
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  6. A. M. Burdennyy
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  8. T. P. Kazubskaya
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  9. A. A. Kubatiev
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  10. N. E. Kushlinskii
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Correspondence to E. A. Braga.

Additional information

Published in Russian in Biokhimiya, 2015, Vol. 80, No. 4, pp. 568–581.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM14-325, February 22, 2015.

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Braga, E.A., Loginov, V.I., Pronina, I.V. et al. 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. Biochemistry Moscow 80, 483–494 (2015). https://doi.org/10.1134/S0006297915040124

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  • DOI: https://doi.org/10.1134/S0006297915040124

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