SCIENTIFIC AND INFORMATION-ANALYTICAL MAGAZINE

ISSN 1024-6177 (Print), ISSN 2618-9615 (Online)

Medical Radiology and Radiation Safety. 2015. Vol. 60. No. 1. P. 5-14

RADIATION BIOLOGY

L.V. Shulenina1, V.F. Mikhailov1, E.V. Ledin2, N.F. Raeva1, G.D. Zasukhina3

Evaluation of P53-Dependent System of Maintaining the Genome Stability by Content of MicroRNA and MRNA in Blood of Cancer Patients

1. A.I. Burnasyan Federal Medical Biophysical Center of FMBA, Moscow, Russia, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. ; 2. Treatment-and-reabilitation Center of Ministry of Health of Russia, Moscow, Russia; 3. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russia

ABSTRACT

Purpose: To explore the content of mature mir125b, mir21, mir34a, mir145, let7a, mir16 and mRNA of P53, MDM2, MDMX genes, modulating activity of p53-dependent system of maintaining the genome stability in blood of cancer patients before and after radiotherapy for evaluation of disease prognosis and identification of the most promising targets for pharmacological correction.

Material and methods: We used the whole blood of patients with prostate cancer, breast cancer, head and neck cancer which was received before and after radiation therapy. The control was the blood of healthy donors. Radiation therapy was carried out on the equipment ROCUS (60Co). The total dose of irradiation was about 70 Gy. The content of the mature microRNA and mRNA was determined using the quantative reverse-transcription real-time PCR with gene-specific primers. Relative expression was calculated according to the method ΔΔCt. Statistical analysis of the results was carried out by the Mann-Whitney and Wilcoxon tests. Data are presented as median and quartiles, normalized to median of control group accepted as 1.

Results: The low expression of MDMX and high content of both mir21 and let7a were found in the blood of prostate cancer patients in comparison with blood of donors. Radiotherapy increased mir34a, but did not influence on another indicators. The breast cancer patients have high level mir145, mir21 and mir 34a before radiotherapy. Expression of MDM2 after radiotherapy declined in blood of these persons. The patients with head and neck cancer revealed significantly high level of mir21, mir145, mir34a and radiotherapy caused an extension of let7a.

Conclusion: The low efficiency of functioning P53- dependent system, maintaining the genome stability is the precondition factor of tumors’ high radioresistance. Inactivation of p53 in cancer cells is due to mutations in the p53 gene, increased activity of the endogenous inhibitors of MDM2, MDMX and balance of mature mir16, 21, 34, 125, 145. It was found the increase of mir145, mir21, mir34a, and let7a content in blood of oncologic patients. It is presumed that the changes of expression these indicators support the information about the effectivity of therapy and for development of p53-dependent-system-drugs.

Key words: radiotherapy, cancer patients, genome stability, p53-dependent system maintaining mir125b, mir21, mir34a, mir145, mir16, let7a, targeted compounds

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For citation: Shulenina LV, Mikhailov VF, Ledin EV, Raeva NF, Zasukhina GD. Evaluation of P53-Dependent System of Maintaining the Genome Stability by Content of MicroRNA and MRNA in Blood of Cancer Patients. Medical Radiology and Radiation Safety. 2015;60(1):5-14. Russian.

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