Abstract
An estimate of relative expression of mature microRNAs assessed in peripheral blood cells in persons chronically exposed to low-dose radiation in the long-term period was performed. The study included people exposed in the 1950s on the Techa River (Southern Urals, Russia). The cumulative red bone marrow doses (RBM) of the persons in the main study group (33 persons) ranged from 77.7 to 2869.8 mGy (mean value of 698.5 mGy). The comparison group consisted of 30 people with RBM dose not exceeding 70 mGy over their lifetime. Reverse transcription of RNA samples was performed using specific stem-loop primers (“stem-loop”). Changes in the relative content of microRNAs were assessed by real-time PCR on the CFX96 detection system (BioRad, United States). Statistical analysis of the results was performed using the Mann–Whitney U criterion. A significant increase in hsa-miR-125b, hsa-miR-181a, and hsa-miR-16-5p content was detected in exposed people after 60 years, and their expression was found to depend on the RBM dose.
REFERENCES
Friedman, R.C., Farh, K.K., Burge, C.B., et al., Most mammalian mRNAs are conserved targets of microRNAs, Genome Res., 2009, vol. 19, no. 1, pp. 92—105. https://doi.org/10.1101/gr.082701.108
Mao, A., Liu, Y., 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. https://doi.org/10.1089/dna.2014.2401
Pashaei, E., Pashaei, E., Ahmady, M., et al., Meta-analysis of miRNA expression profiles for prostate cancer recurrence following radical prostatectomy, PLoS One, 2017, vol. 12, no. 6, р. e00179543. https://doi.org/10.1371/journal.pone.0179543
Adhami, M., Haghdoost, A.A., Sadeghi, B., et al., Candidate miRNAs in human breast cancer biomarkers: a systematic review, Breast Cancer, 2018, vol. 25, no. 2, pp. 198—205. https://doi.org/10.1007/s12282-017-0814-803
Pardini, B., De Maria, D., Francavilla, A., et al., MicroRNAs as markers of progression in cervical cancer: a systematic review, BMC Cancer, 2018, vol. 18, no. 1, p. 696. https://doi.org/10.1186/s12885-018-4590-4
Shao, C., Yang, F., Qin, Z., et al., The value of miR-155 as a biomarker for the diagnosis and prognosis of lung cancer: a systematic review with meta-analysis, BMC Cancer, 2019, vol. 19, no. 1, p. 1103. https://doi.org/10.1186/s12885-019-6297-6
Romakina, V.V., Zhirov, I.V., Nasonova, S.N., Zaseeva, A.V., Kochetov, A.G., Liang, O.V., and Tereshchenko, S.N., MicroRNAs as biomarkers of cardiovascular diseases, Kardiologiia, 2018, vol. 58, no. 1, pp. 66—71. https://doi.org/10.18087/cardio.2018.1.10083
Otsuka, M., Kishikawa, T., Yoshikawa, T., et al., MicroRNAs and liver disease, J. Hum. Genet., 2016, vol. 62, pp. 75—80. https://doi.org/10.1038/jhg.2016.53
Zhang, Y., Jia, Y., Zheng, R., et al., Plasma microRNA-122 as a biomarker for viral-, alcohol-, and chemical-related hepatic diseases, Clin. Chem., 2010, vol. 56, no. 12, pp. 1830—1838. https://doi.org/10.1373/clinchem.2010.147850
Metheetrairut, C. and Slack, F.J., MicroRNAs in the ionizing radiation response and in radiotherapy, Curr. Opin. Genet. Dev., 2013, vol. 23, no. 1, pp. 2—19. https://doi.org/10.1016/j.gde.2013.01.002
Jacob, N.K., Cooley, J.V., Yee, T.N., et al., Identification of sensitive serum microRNA biomarkers for radiation biodosimetry, PLoS One, 2013, vol. 8, no. 2, р. 57603. https://doi.org/10.1371/journal.pone.0057603
Chaudhry, M.A., Omaruddin, R.A., Kreger, B., et al., MicroRNA responses to chronic or acute exposures to low dose ionizing radiation, Mol. Biol. Rep., 2012, vol. 39, no. 7, pp. 7549—7558. https://doi.org/10.1007/s11033-012-1589-9
Simone, N.L., Soule, B.P., Ly, D., et al., Ionizing radiation-induced oxidative stress alters miRNA expression, PLoS One, 2009, vol. 4, р. 6377. https://doi.org/10.1371/journal.pone.0006377
Shin, S., Cha, H.J., Lee, E.M., et al., Alteration of miRNA profiles by ionizing radiation in A549 human non-small cell lung cancer cells, Int. J. Oncol., 2009, vol. 35, no. 1, pp. 81—86.
Chaudhry, M.A., Real-time PCR analysis of microRNA expression in ionizing radiation-treated cells, Cancer Biother. Radiopharm., 2009, vol. 24, no. 1, pp. 49—56. https://doi.org/10.1089/cbr.2008.0513
Song, M., Xie, D., Gao, S., et al., A biomarker panel of radiation-upregulated miRNA as signature for ionizing radiation exposure, Life (Basel), 2020, vol. 10, no. 12, р. 361. https://doi.org/10.3390/life10120361
Templin, T., Paul, S., Amundson, S.A., et al., Radiation-induced microRNA expression changes in peripheral blood cells of radiotherapy patients, Int. J. Radiat. Oncol., Biol., Phys., 2011, vol. 80, no. 2, р. 54957. https://doi.org/10.1016/j.ijrobp.2010.12.061
Weidhaas, I., Babar, S.M., Nallur, P., et al., MicroRNAs as potential agents to alter resistance to cytotoxic anticancer therapy, Cancer Res., 2007, vol. 67, no. 23, pp. 11111—11116.
Maes, O.C., An, J., Sarojini, H., et al., Changes in microRNA expression patterns in human fibroblasts after low-LET radiation, J. Cell. Biochem., 2008, vol. 105, no. 3, pp. 824—834. https://doi.org/10.1002/jcb.21878
Templin, T., Paul, S., Amundson, S.A., et al., Radiation-induced micro-RNA expression changes in peripheral blood cells of radiotherapy patients, Int. J. Radiat. Oncol., Biol., Phys., 2011, vol. 80, no. 2, pp. 549—557. https://doi.org/10.1016/j.ijrobp.2010.12.061
Lacombe, J., Sima, C., Amundson, S.A., and Zenhausern, F., Candidate gene biodosimetry markers of exposure to external ionizing radiation in human blood: a systematic review, PLoS One, 2018, vol. 13, no. 6, р. e0198851. https://doi.org/10.1371/journal.pone.0198851
Jacob, N.K., Cooley, J.V., Yee, T.N., et al., Identification of sensitive serum microRNA biomarkers for radiation biodosimetry, PLoS One, 2013, vol. 8, no. 2, р. e57603. https://doi.org/10.1371/journal.pone.0057603
Chen, G., Zhu, W., Shi, D., et al., MicroRNA-181a sensitizes human malignant glioma U87MG cells to radiation by targeting Bcl-2, Oncol. Rep., 2010, vol. 23, no. 4, pp. 997—1003. https://doi.org/10.3892/or_00000725
Beer, L., Seemann, R., Ristl, R., et al., High dose ionizing radiation regulates microRNA and gene expression changes in human peripheral blood mononuclear cells, BMC Genomics, 2014, vol. 15, р. 814. https://doi.org/10.1186/1471-2164-15-814
Sun, Y., Hawkins, P.G., Bi, N., et al., Serum microRNA signature predicts response to high-dose radiation therapy in locally advanced non-small cell lung cancer, Int. J. Radiat. Oncol., Biol., Phys., 2018, vol. 100, no. 1, pp. 107—114. https://doi.org/10.1016/j.ijrobp.2017.08.039
Silkin, S.S., Krestinina, L.Yu., Startsev, V.N., and Akleev, A.V., Ural cohort of emergency-irradiated population, Med. Ekstremal’nykh Situat., 2019, vol. 21, no. 3, pp. 393—402.
Degteva, M.O., Napier, B.A., Tolstykh, E.I., et al., Enhancements in the Techa River dosimetry system: TRDS-2016D code for reconstruction of deterministic estimates of dose from environmental exposures, Health Phys., 2019, vol. 117, no. 4, pp. 378—387. https://doi.org/10.1097/HP.0000000000001067
Livak, K.J. and Schmittgen, T.D., Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)), Methods, 2001, vol. 25, no. 4, pp. 402—408. https://doi.org/10.1006/meth.2001.1262
Riolo, G., Cantara, S., Marzocchi, C., and Ricci, C., miRNA targets: from prediction tools to experimental validation, Methods Protoc., 2020, vol. 4, no. 1. https://doi.org/10.3390/mps4010001
Stroynowska-Czerwinska, A., Fiszer, A., and Krzyzosiak, W.J., The panorama of miRNA-mediated mechanisms in mammalian cells, Cell. Mol. Life Sci., 2014, vol. 71, no. 12, pp. 2253—2270. https://doi.org/10.1007/s00018-013-1551-6
Aqeilan, R.I., Calin, G.A., and Croce, C.M., miR-15a and miR-16-1 in cancer: discovery, function and future perspectives, Cell Death Differ., 2010, vol. 17, no. 2, pp. 215—220. https://doi.org/10.1038/cdd.2009.69
Chen, G., Zhu, W., Shi, D., et al., MicroRNA-181a sensitizes human malignant glioma U87MG cells to radiation by targeting Bcl-2, Oncol. Rep., 2010, vol. 23, no. 4, pp. 997—1003. https://doi.org/10.3892/or_00000725
Makhotkin, M.A., Chebotarev, D.A., Tyutyakina, M.G., et al., The role of microRNAs in the development of radioresistance of prostate cancer cells (experimental study), Onkourologiia, 2021, vol. 17, no. 4, pp. 85—93. https://doi.org/10.17650/1726-9776-2021-17-4-85-93
Shulenina, L.V., Mikhailov, V.F., Vasilyeva, I.M., et al., Genes- and noncoding RNA-expression profiles in tissue bioptats and blood cells of patients with different pathology after radiation exposure, Vestn. Voronezh. Gos. Univ., Ser. Khim. Biol. Farm., 2019, no. 1, pp. 103—109.
Yang, D., Zhan, M., Chen, T., et al., miR-125b-5p enhances chemotherapy sensitivity to cisplatin by down-regulating Bcl2 in gallbladder cancer, Sci. Rep., 2017, vol. 7, р. 43109. https://doi.org/10.1038/srep43109
Nikiforov, V.S., Blinova, E.A., and Akleyev, A.V., Transcriptional activity of cell cycle and apoptosis genes in chronically irradiated individuals with an increased frequency of TCR-mutant lymphocytes, Radiats. Risk, 2020, vol. 29, no. 2, pp. 89—100.
Funding
This work was financed within the framework of the federal target program “Ensuring Nuclear and Radiation Safety for 2016–2020 and for the Period up to 2030.”
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest. The authors declare that they have no conflict of interest.
Statement of compliance with standards of research involving humans as subjects. All procedures performed in research with human participants comply with the ethical standards of the institutional and/or national committee on research ethics and the 1964 Declaration of Helsinki and its subsequent amendments or comparable ethical standards.
Informed consent was obtained from each of the participants included in the study.
Rights and permissions
About this article
Cite this article
Yanishevskaya, M.A., Blinova, E.A. & Akleyev, A.V. Effect of Chronic Radiation Exposure on Human MicroRNA Expression. Russ J Genet 59, 1050–1057 (2023). https://doi.org/10.1134/S1022795423100150
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1022795423100150