Skip to main content
Log in

The miRNA as human cell gene activity regulator after ionizing radiation

  • Review and Theoretical Articles
  • Published:
Russian Journal of Genetics Aims and scope Submit manuscript

Abstract

This review presents analysis of the literature and our own research with respect to the role of miRNAs in the regulation of activity (expression) of genes controlling cellular homeostasis in human cells when exposed to ionizing radiation. Human cells, on one hand, can have increased resistance to radiation, which hinders the effectiveness of tumor treatment in radiotherapy. On the other hand, increased sensitivity to radiation may be accompanied by the development of several pathologies, including tumorigenesis. This paper examines the role of specific miRNAs in the formation of radioresistance and radiosensitivity of human cells and their impact on the respective target genes. Separate sections are devoted to the role of different miRNAs in radiation therapy of tumors of different localization, as well as their role in the bystander effect. A special section highlights features of gene activity and its regulators, miRNAs, in radiosensitive cells in patients with Down syndrome. The final section provides information about new approaches to change miRNA expression and, accordingly, their target genes by the action of plant and synthetic drugs (crown compounds) which reduce damaging effects of mutagens. It is assumed that antimutagens affecting the expression levels of miRNAs and structural genes may be used to correct the increase and decrease in cellular radioresponse, reducing the risk of development of pathological processes, including tumorigenesis.

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

Access this article

Subscribe and save

Springer+
from $39.99 /Month
  • Starting from 10 chapters or articles per month
  • Access and download chapters and articles from more than 300k books and 2,500 journals
  • Cancel anytime
View plans

Buy Now

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Brenner, D. and Hall, E., Computed tomography–an increasing source of radiation exposure, New Engl. J. Med., 2007, vol. 357, pp. 2277–2284.

    Article  CAS  PubMed  Google Scholar 

  2. Lowe Xin, Bhattacharya, S., Marchetti, F., et al., Early brain response to low–dose radiation exposure involved molecular networks and pathways associated with cognitive functions, advanced aging and Alzheimer, sdisease, Rad. Res., 2009, vol. 171, pp. 53–65.

    Article  CAS  Google Scholar 

  3. Olial, C. and Li-Xi Yang, Radioprotectans to reduce the risk of radiation-induced carcinogenesis, Int. J. Rad. Biol., 2014, vol. 90, no. 3, pp. 203–213.

    Article  Google Scholar 

  4. Yen, P., Lin, I., Chang, W., et al., Risk factors of depression after prolonged low-dose rate environmental radiation exposure, Int. J. Rad. Biol., 2014, vol. 90, no. 10, pp. 854–866.

    Article  Google Scholar 

  5. Druzhinin, V.G., Volkov, V.A., Glushkov, A.N., et al., The role of polymorphisms of genes reparations in assessing the human genome sensitivity to the effects of excessive radon concentrations, Gig. Sanit., 2011, no. 5, pp. 26–30.

    Google Scholar 

  6. Jeggo, P., The role of DNA damage response mechanisms after low–dose radiation exposure and a consideration of potentially sensitive individual, Rad. Res., 2010, vol. 174, pp. 825–832.

    Article  CAS  Google Scholar 

  7. Korpela, E., Vesprini, D., and Lin, S., MicroRNA in radiotherapy: miRage or miRador?, Br. J. Cancer, 2015, vol. 112, pp. 777–782.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Braga, E.A., Khodyrev, D.S., Loginov, V.I., et al., Methylation in the regulation of the expression of chromosome 3 and microRNA genes in clear-cell renal cell carcinomas, Russ. J. Genet., 2015, vol. 51, no. 6, pp. 566–581.

    Article  CAS  Google Scholar 

  9. Metheetrairut, C. and Slank, F., MicroRNA in the ionizing radiation response and in radiotherapy, Curr. Opin. Genet. Dev., 2013, vol. 23, pp. 12–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Cellini, F., Morganti, A., Gorovesi, D., et al., Role of microRNA in response to ionizing radiations: evidences and potential impact on clinical practice for radiotherapy, Molecules, 2014, vol. 19, pp. 5379–5401.

    Article  PubMed  Google Scholar 

  11. Gandellini, P., Rancati, T., Valdagni, R., et al., MicroRNAs in tumor radiation response: bystanders or participants?, Trends Mol. Med., 2014, vol. 20, no. 9, pp. 529–539.

    Article  CAS  PubMed  Google Scholar 

  12. Friedman, R., Farh, K., Burge, C., et al., Most mammalian mRNA are conserved targets of micro RNAs, Genome Res., 2009, vol. 19, pp. 92–105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Yu, Q., Li, B., Li, P., et al., Plasma microRNA to predict the response of radiotherapy in esophageal squamous cell carcinoma patients, Am. J. Transl. Res., 2015, vol. 7, pp. 2060–2070.

    PubMed  PubMed Central  Google Scholar 

  14. Czochor, J.R. and Glazer, P.M., MicroRNAs in cancer cells response to ionizing radiation, Antioxid. Redox Signaling, 2014, vol. 21, no. 2, pp. 293–312.

    Article  CAS  Google Scholar 

  15. Barjaktarovic, Z., Anastasov, N., Azimzadeh, A., et al., Integrative proteomic and microRNA analysis of primary human coronary artery endothelial cells exposed to low-dose gamma radiation, Rad. Environ. Biophys., 2013, vol. 52, pp. 87–98.

    Article  CAS  Google Scholar 

  16. Gong, P., Zhang, T., He, D., et al., MicroRNA-145 modulates tumor sensitivity to radiation in prostate cancer, Rad. Res., 2015, vol. 184, pp. 563–569.

    Article  Google Scholar 

  17. Yang, Y., Xu, X., and Hao, Y., Research of the relationship between radiotherapy and microRNAs, J. Clin. Oncol., 2012, vol. 11, no. 5, pp. 285–289.

    Google Scholar 

  18. Xu, S., Wang, Y., Ding, N., et al., Exome-mediated microRNA transfer plays a role in radiation-induced bystander effect, RNA Biol., 2015, p. 1100795.

    Google Scholar 

  19. Mao, A., Liu, G., Zhang, H., et al., MicroRNA expression and biogenesis in cellular response to ionizing radiation, DNA Cell Biol., 2014, vol. 33, no. 10, pp. 667–679.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Dressman, H.K., Muramoto, G.G., Chao, N.J., et al., Gene expression signatures that predict radiation exposure in mice and humans, PLoS Med., 2007, vol. 4. e106

    Article  PubMed  PubMed Central  Google Scholar 

  21. Bi, N., Schipper, M., Stanton, P., et al., Serum miRNA signature to identify a patient’s resistance to high-dose radiation therapy for unresectable non-small cell lung cancer, J. Clin. Oncol., 2013, vol. 31, pp. 75–80.

    Google Scholar 

  22. Ke, G., Liang, L., Yang, Y., et al., MiR181a confers resistance of cervical cancer to radiation therapy through targeting the proapoptopic PRKCD gene, Oncogene, 2013, vol. 32, pp. 3019–3027.

    Article  CAS  PubMed  Google Scholar 

  23. Girardi, C., Pitta, C., Casara, S., et al., Analysis of miRNA and mRNA expression profiles alterations in ionizing radiation response of human lymphocytes under modeled microgravity, PLoS One, 2012, vol. 7. e31293

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Saleh, A.D., Savage, J.E., Cao, L., et al. Cellular stress induced alteration in microRNA let-7a and let-7b expression are dependent on p53, PLoS One, 2011, vol. 6. e24429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Zhang, J., Sun, Q., Zhang, Z., et al., Loss of microRNA-143/145 disturbs cellular growth and apoptosis of human epithelial cancer by impairing the MDM2-p53 feedback loop, Oncogene, 2013, vol. 32, no. 1, pp. 61–69.

    Article  PubMed  Google Scholar 

  26. Le, M.T., The, C., et al., MicroRNA-125b a novel negative regulator of p53, Genes Dev., 2009, vol. 23, pp. 862–876.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hu, W., Chan, C.S., Wu, R., et al., Negative regulation of tumor suppressor p53 by microRNA miR 504, Mol. Cell, 2010, vol. 38, no. 5, pp. 689–699.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kumar, M., Lu, Z., Takwi, A.A., et al., Negative regulation of the tumor suppressor p53 gene be microRNAs, Oncogene, 2011, vol. 30, pp. 843–853.

    Article  CAS  PubMed  Google Scholar 

  29. Brachova, P., Mueting, S., Devor, E., et al., Oncomorphic TP53 mutations in gynecologic cancer lose the normal protein: protein interactions with microRNA microprocessing complex, J. Cancer Ther., 2014, vol. 5, pp. 506–516.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Mendell, J., miRiad roles for the miR-17–92 cluster in development and disease, Cell, 2008, vol. 133, pp. 217–222.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Mert, U., Ozgur, E., Tiryakioglu, D., et al., Induction of p-53-inducible microRNA-34 by gamma-radiation and bleomycin are different, Front. Genet., 2012, vol. 3, pp. 1–3.

    Article  Google Scholar 

  32. Moskwa, P., Buffa, F., Pan, G., et al., miR-182–mediated downregulation of BRCA1 impacts DNA repair and sensitivity to PARP inhibitors, Mol. Cell, 2011, vol. 41, pp. 210–220.

    Article  CAS  PubMed  Google Scholar 

  33. Yan, D., Ng, W., Zhang, X., et al., Targeting DNAPKcs and ATM with miR-101 sensitized tumors to radiation, PLoS One, 2010, vol. 5. e11397

    Article  PubMed  PubMed Central  Google Scholar 

  34. Wright, C., Dan, T., Dicker, A., et al., MicroRNAs: the shot link between cancer and RT-induced DNA damage respons, Front. Oncol., 2014, vol. 4, pp. 1–3.

    Article  Google Scholar 

  35. Tarasov, V.A., Matishov, D.G., Shin, E.F., et al., Coordinated aberrant expression of miRNAs in colon cancer, Russ. J. Genet., 2014, vol. 50, no. 10, pp. 1090–1101.

    Article  CAS  Google Scholar 

  36. Zhao, L., Bode, A., Cao, G., et al., Regulatory mechanisms and clinical perspectives of microRNA in tumor radiosensitive, Carcinogenesis, 2012, vol. 33, pp. 2220–2227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Iorio, M.V., Ferrasin, M., Liu, C., et al., MicroRNA gene expression deregulation in human breast cancer, Cancer Res., 2005, vol. 65, pp. 7065–7070.

    Article  CAS  PubMed  Google Scholar 

  38. Bonci, D., Coppola, V., Musumeci, V., et al., The miR-15a-miR-16-1 cluster controls prostate cancer by targeting multiple oncogenic activities, Nat. Med., 2008, vol. 14, pp. 1271–1277.

    Article  CAS  PubMed  Google Scholar 

  39. Salnikova, L.E., Clinicopathologic characteristics of brain tumors are associated with the presence and patterns of TP53 mutations: evidence from the IARC TP53 Database, Neuromol. Med., 2014, vol. 16, pp. 431–447.

    Article  CAS  Google Scholar 

  40. Nadiminty, N., Tummala, R., Lou, W., et al., MicroRNA let-7c suppressed androgen receptor expression and activity via regulation of Myc expression in prostate cancer cells, J. Biol. Chem., 2012, vol. 287, no. 2, pp. 1527–1537.

    Article  CAS  PubMed  Google Scholar 

  41. Huang, X., Taeb, S., Jahangiri, S., et al., MicroRNA-95 mediates radioresistance in tumor by targeting the sphingolipid phosphatase SGPP1, Cancer Res., 2013, vol. 73, no. 23, pp. 6972–6986.

    Article  CAS  PubMed  Google Scholar 

  42. Arora, H., Qureshi, R., Jin, S., et al., Mir-9 and let-7g enhance the sensitivity to ionizing radiation by suppression of NF[kappa]B1, Exp. Mol. Med., 2011, vol. 43, pp. 298–304.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Shulenina, L.V., Galstyan, I.A., Nadezhdina, N.M., et al., The expression of mature miRNAs involved in the functioning of the p53-dependent system to preserve the stability of the genome in individuals exposed to clinically relevant doses, Sarat. Nauchno-Med. Zh., 2014, vol. 10, no. 4, pp. 5–14.

    Google Scholar 

  44. Li, B., Shi, X., Nori, D., et al., Down-regulated of microRNA106b is involved in pz1-mediated cell cycle arrest in response to radiation in prostate cancer cells, Prostate, 2011, vol. 71, pp. 567–574.

    Article  CAS  PubMed  Google Scholar 

  45. Shulenina, L.V., Mikhailov, V.F., Ledin, E.V., et al., Evaluating the effectiveness of the p53-dependent system of genome stability based on microRNA and mRNA content in the blood of cancer patients, Med. Radiol. Radiats. Bezop., 2015, vol. 60, no. 1, pp. 5–14.

    Google Scholar 

  46. Xu, S., Ding, N., Pei, H., et al., MiR-21 is involved in radiation-induced bystander effect, RNA Biol., 2014, vol. 11, pp. 1161–1170.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Skog, J., Wurdinger, T., Rijn, S., et al., Glioblastoma microvesicles transport RNA and proteins that promote tumor growth and provide diagnostic biomarkers, Nature, 2008, vol. 10, pp. 1470–1476.

    CAS  Google Scholar 

  48. Talor, D. and Geral-Talor, C., MicroRNA signature of tumor-derived exosomes as diagnostic biomarker of ovarian cancer, Ginecol. Oncol., 2008, vol. 110, pp. 13–21.

    Article  Google Scholar 

  49. Ohshima, S., Inoue, K., Fujiwara, A., et al., Let-7 microRNA family is selectively secreted into the extracellular environment via exosomes in a metastatic gastric cell line, PLoS One, 2010, vol. 5. e347

    Google Scholar 

  50. Zasukhina, G.D., Shagirova, Zh.M., Reutova, N.V., et al., The expression of genes that control cell homeostasis in patients with Down’s syndrome, Tekhnol. Zhivikh Syst., 2013, vol. 10, no. 7, pp. 38–44.

    CAS  Google Scholar 

  51. Zasukhina, G.D., Mikhailov, V.F., Vasil’eva, I.M., and Shulenina, L.V., The cells of patients with Down’s syndrome–a model for studying the mechanisms of carcinogenesis, hypersensitivity to gene toxicants, and antimutagenesis, Usp. Sovrem. Biol., 2016, vol. 136, no. 2, pp. 126–142.

    Google Scholar 

  52. Murley, J., Kataoka, G., Miller, R., et al., SOD-2 mediated effects induced by WR1065 and low-dose ionizing radiation on micronucleus formation in RKO human colon carcinoma cells, Rad. Res., 2011, vol. 175, pp. 57–65.

    Article  CAS  Google Scholar 

  53. Artacho-Cordon, F., Rios-Arrabal, S., Olivares-Urbanj, M.A., et al., Valproic acid modulated radiation-enhanced matrix metalloproteinase activity and invasion of breast cancer cells, Int. J. Rad. Biol., 2015, vol. 91, no. 12, pp. 946–956.

    Article  CAS  PubMed  Google Scholar 

  54. Liao, J., Zhou, X., Zhang, Yu, et al., A new link of p53-family with cancer and Down syndrome, Cell Cycle, 2012, vol. 11, pp. 2624–2630.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Zasukhina, G.D., Vasil’eva, I.M., Shagirova, Zh.M., et al., Comparison of the effects of antimutagens and adapting factors in radioresistant and radiosensitive cells in connection with the protein and gene polymorphism, Tekhnol. Zhivikh Syst., 2009, vol. 6, no. 1, pp. 3–13.

    CAS  Google Scholar 

  56. Zasukhina, G.D., Semyachkina, A.N., Vasil’eva, I.M., et al., Comparison of the antimutagenic activities of natural and synthetic substances in irradiated repairdefective human cells, Dokl. Biol. Sci., 2006, vol. 408, no. 1–6, pp. 269–271.

    Article  CAS  PubMed  Google Scholar 

  57. Kralj, M., Tusec-Bozic, L., and Erkenec, L., Biomedical potentials of crawn ethers: prospective antitumor agents, Chem. Med. Chem., 2008, vol. 3, pp. 1478–1492.

    Article  CAS  PubMed  Google Scholar 

  58. Mikhailov, V.F., Shishkina, A.A., Vasilyeva, I.M., Zasukhina, G.D., Shulenina, L.V., Raeva, N.F., Rogozhin, E.A., Startsev, M.I., Zasukhina, G.D., Gromov, S.P., and Alfimov, M.V., Comparative analysis of natural and synthetic antimutagens as regulators of gene expression in human cells under exposure to ionizing radiation, Russ. J. Genet., 2015, vol. 51, no. 2, pp. 130–137.

    Article  CAS  Google Scholar 

  59. Odintsova, T.I., Vasil’eva, I.M., Zasukhina, G.D., and Korostyleva, T.V., Antimutagenic activity of wheat ß-purothionin Tk-AMP-BP, Russ. J. Genet., 2011, vol. 47: 1128.

    Article  CAS  Google Scholar 

  60. Rastogi, L., Feroz, S., Pandey, B., et al., Protection against radiation oxidative damage by an ethanolic extract of Nigella sativa L., Int. J. Biol., 2010, vol. 86, no. 9, pp. 719–731.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to V. F. Mikhailov.

Additional information

Original Russian Text © V.F. Mikhailov, L.V. Shulenina, I.M. Vasilyeva, M.I. Startsev, G.D. Zasukhina, 2017, published in Genetika, 2017, Vol. 53, No. 3, pp. 265–278.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mikhailov, V.F., Shulenina, L.V., Vasilyeva, I.M. et al. The miRNA as human cell gene activity regulator after ionizing radiation. Russ J Genet 53, 285–296 (2017). https://doi.org/10.1134/S1022795417020077

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1022795417020077

Keywords