Skip to main content
Log in

Novel miRNA genes methylated in lung tumors

  • Short Communications
  • Published:
Russian Journal of Genetics Aims and scope Submit manuscript

Abstract

MicroRNAs play an important role in the regulation of expression of many genes and are involved in carcinogenesis. The regulation of miRNA gene expression can involve the methylation of promoter CpG islands. In this work, the methylation of six miRNA genes (mir-107, mir-125b-1, mir-130b, mir-137, mir-375, and mir-1258) in non-small-cell lung cancer (NSCLC) was studied for the first time by methylation-specific PCR using a representative set of specimens (39 cases). Four new genes (mir-125b-1, mir-137, mir-375, and mir-1258) methylated in primary NSCLC tumors were identified with frequencies of 56, 31, 56, and 36%, respectively. The frequencies of miRNA promoter methylation in DNA of tumors and histologically normal tissues differed significantly (P ≤ 0.05 by Fisher’s test). In lung tissues of 20 donors without a history of cancer, these genes were only methylated in a few cases. It was also shown that the previously unstudied promoter CpG islands of mir-107 and mir-130b were not methylated in NSCLC. The frequencies of mir-125b-1 and mir-137 methylation were shown for the first time to correlate with NSCLC progression (clinical stage and metastasis).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

References

  1. Mukeriya, A.F. and Zaridze, D.G., Epidemiology and prophylaxis of lung cancer, Vestn. Ross. Oncol. Nauchn. Tsentr im. N.N. Blokhina Ross. Akad. Med. Nauk, 2010, vol. 21, no. 3, pp. 3–12.

    Google Scholar 

  2. Jones, P.A., Functions of DNA methylation: islands, start sites, gene bodies and beyond, Nat. Rev. Genet., 2012, vol. 13, no. 7, pp. 484–492.

    Article  PubMed  CAS  Google Scholar 

  3. Kato, M. and Slack, F.J., microRNAs: small molecules with big roles—C. elegans to human cancer, Biol. Cell, 2008, vol. 100, no. 2, pp. 71–81.

    Article  PubMed  CAS  Google Scholar 

  4. Kunej, T., Godnic, I., Ferdin, J., et al., Epigenetic regulation of microRNAs in cancer: an integrated review of literature, Mutat. Res., 2011, vol. 717, nos. 1–2, pp. 77–84.

    PubMed  CAS  Google Scholar 

  5. Qi, J. and Mu, D., microRNAs and lung cancers: from pathogenesis to clinical implications, Front. Med., 2012, vol. 6, no. 2, pp. 134–155.

    Article  PubMed  Google Scholar 

  6. Sato, F., Tsuchiya, S., Meltzer, S.J., et al., microRNAs and epigenetics, FEBS J., 2011, vol. 278, no. 10, pp. 1598–1609.

    Article  PubMed  CAS  Google Scholar 

  7. Khodyrev, D.S., Pronina, I.V., and Rykov, S.V., et al., Involvement of methylation of group of miRNA genes in regulation of expression of RAR-beta2 and NKIRAS1 target genes in lung cancer, Mol. Biol. (Moscow), 2012, vol. 46, no. 5, pp. 693–704.

    Article  CAS  Google Scholar 

  8. Lee, K.H., Lotterman, C., Karikari, C., et al., Epigenetic silencing of microRNA miR-107 regulates cyclin-dependent kinase 6 expression in pancreatic cancer, Pancreatology, 2009, vol. 9, no. 3, pp. 293–301.

    Article  PubMed  CAS  Google Scholar 

  9. Soto-Reyes, E., González-Barrios, R., Cisneros-Soberanis, F., et al., Disruption of CTCF at the miR-125b1 locus in gynecological cancers, BMC Cancer, 2012, vol. 12, no. 40.

    Google Scholar 

  10. Yang, C., Cai, J., Wang, Q., et al., Epigenetic silencing of miR-130b in ovarian cancer promotes the development of multidrug resistance by targeting colony-stimulating factor 1, Gynecol. Oncol., 2012, vol. 124, no. 2, pp. 325–334.

    Article  PubMed  CAS  Google Scholar 

  11. Balaguer, F., Link, A., Lozano, J.J., et al., Epigenetic silencing of miR-137 is an early event in colorectal carcinogenesis, Cancer Res., 2010, vol. 70, no. 16, pp. 6609–6618.

    Article  PubMed  CAS  Google Scholar 

  12. Zhang, Y., Yan, L.X., Wu, Q.N., et al., miR-125b is methylated and functions as a tumor suppressor by regulating the ETS1 proto-oncogene in human invasive breast cancer, Cancer Res., 2011, vol. 71, no. 10, pp. 3552–3562.

    Article  PubMed  CAS  Google Scholar 

  13. Liu, H., Chen, X., Gao, W., et al., The expression of heparanase and microRNA-1258 in human non-small cell lung cancer, Tumour Biol., 2012, vol. 33, no. 5, pp. 1327–1334.

    Article  PubMed  CAS  Google Scholar 

  14. Zhang, L., Sullivan, P.S., Goodman, J.C., et al., microRNA-1258 suppresses breast cancer brain metastasis by targeting heparanase, Cancer Res., 2011, vol. 71, no. 3, pp. 645–654.

    Article  PubMed  CAS  Google Scholar 

  15. Dacic, S., Kelly, L., Shuai, Y., et al., miRNA expression profiling of lung adenocarcinomas: correlation with mutational status, Mod. Pathol., 2010, vol. 23, no. 12, pp. 1577–1582.

    Article  PubMed  CAS  Google Scholar 

  16. Zhu, X., Li, Y., Shen, H., et al., miR-137 inhibits the proliferation of lung cancer cells by targeting Cdc42 and Cdk6, FEBS Lett., 2013, vol. 587, no. 1, pp. 73–81.

    Article  PubMed  CAS  Google Scholar 

  17. Friboulet, L., Barrios-Gonzales, D., Commo, F., et al., Molecular characteristics of ERCC1-negative versus ERCC1-positive tumors in resected NSCLC, Clin. Cancer Res., 2011, vol. 17, no. 17, pp. 5562–5572.

    Article  PubMed  CAS  Google Scholar 

  18. Li, Y., Jiang, Q., Xia, N., et al., Decreased expression of microRNA-375 in nonsmall cell lung cancer and its clinical significance, J. Int. Med. Res., 2012, no. 5, pp. 1662–1669.

    Google Scholar 

  19. Ponomareva, A.A., Rykova, E.Yu., and Cherdyntseva, N.V., et al., Molecular and genetic markers in diagnostics of lung cancer, Mol. Biol. (Moscow), 2011, vol. 45, no. 2, pp. 175–189.

    Article  Google Scholar 

  20. Hsu, H.S., Chen, T.P., Hung, C.H., et al., Characterization of a multiple epigenetic marker panel for lung cancer detection and risk assessment in plasma, Cancer, 2007, vol. 110, no. 9, pp. 2019–2026.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to S. V. Rykov.

Additional information

Original Russian Text © S.V. Rykov, D.S. Khodyrev, I.V. Pronina, T.P. Kazubskaya, V.I. Loginov, E.A. Braga, 2013, published in Genetika, 2013, Vol. 49, No. 7, pp. 896–901.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rykov, S.V., Khodyrev, D.S., Pronina, I.V. et al. Novel miRNA genes methylated in lung tumors. Russ J Genet 49, 782–786 (2013). https://doi.org/10.1134/S1022795413070119

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1022795413070119

Keywords

Navigation