JOURNAL DESCRIPTION
The Medical Radiology and Radiation Safety journal ISSN 1024-6177 was founded in January 1956 (before December 30, 1993 it was entitled Medical Radiology, ISSN 0025-8334). In 2018, the journal received Online ISSN: 2618-9615 and was registered as an electronic online publication in Roskomnadzor on March 29, 2018. It publishes original research articles which cover questions of radiobiology, radiation medicine, radiation safety, radiation therapy, nuclear medicine and scientific reviews. In general the journal has more than 30 headings and it is of interest for specialists working in thefields of medicine¸ radiation biology, epidemiology, medical physics and technology. Since July 01, 2008 the journal has been published by State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency. The founder from 1956 to the present time is the Ministry of Health of the Russian Federation, and from 2008 to the present time is the Federal Medical Biological Agency.
Members of the editorial board are scientists specializing in the field of radiation biology and medicine, radiation protection, radiation epidemiology, radiation oncology, radiation diagnostics and therapy, nuclear medicine and medical physics. The editorial board consists of academicians (members of the Russian Academy of Science (RAS)), the full member of Academy of Medical Sciences of the Republic of Armenia, corresponding members of the RAS, Doctors of Medicine, professor, candidates and doctors of biological, physical mathematics and engineering sciences. The editorial board is constantly replenished by experts who work in the CIS and foreign countries.
Six issues of the journal are published per year, the volume is 13.5 conventional printed sheets, 88 printer’s sheets, 1.000 copies. The journal has an identical full-text electronic version, which, simultaneously with the printed version and color drawings, is posted on the sites of the Scientific Electronic Library (SEL) and the journal's website. The journal is distributed through the Rospechat Agency under the contract № 7407 of June 16, 2006, through individual buyers and commercial structures. The publication of articles is free.
The journal is included in the List of Russian Reviewed Scientific Journals of the Higher Attestation Commission. Since 2008 the journal has been available on the Internet and indexed in the RISC database which is placed on Web of Science. Since February 2nd, 2018, the journal "Medical Radiology and Radiation Safety" has been indexed in the SCOPUS abstract and citation database.
Brief electronic versions of the Journal have been publicly available since 2005 on the website of the Medical Radiology and Radiation Safety Journal: http://www.medradiol.ru. Since 2011, all issues of the journal as a whole are publicly available, and since 2016 - full-text versions of scientific articles. Since 2005, subscribers can purchase full versions of other articles of any issue only through the National Electronic Library. The editor of the Medical Radiology and Radiation Safety Journal in accordance with the National Electronic Library agreement has been providing the Library with all its production since 2005 until now.
The main working language of the journal is Russian, an additional language is English, which is used to write titles of articles, information about authors, annotations, key words, a list of literature.
Since 2017 the journal Medical Radiology and Radiation Safety has switched to digital identification of publications, assigning to each article the identifier of the digital object (DOI), which greatly accelerated the search for the location of the article on the Internet. In future it is planned to publish the English-language version of the journal Medical Radiology and Radiation Safety for its development. In order to obtain information about the publication activity of the journal in March 2015, a counter of readers' references to the materials posted on the site from 2005 to the present which is placed on the journal's website. During 2015 - 2016 years on average there were no more than 100-170 handlings per day. Publication of a number of articles, as well as electronic versions of profile monographs and collections in the public domain, dramatically increased the number of handlings to the journal's website to 500 - 800 per day, and the total number of visits to the site at the end of 2017 was more than 230.000.
The two-year impact factor of RISC, according to data for 2017, was 0.439, taking into account citation from all sources - 0.570, and the five-year impact factor of RISC - 0.352.
Medical Radiology and Radiation Safety. 2025. Vol. 70. № 2
DOI:10.33266/1024-6177-2025-70-2-27-34
P.A. Malakhov1, V.V. Maximov2, M.V. Pustovalova1, A.V. Smirnova1, Z. Nofal1,
V. Saburov3, A.N. Osipov1, D.V. Kuzmin1, S.V. Leonov1, 4
MiR-16-1-3p and miR-16-2-3p Overexpression Confers Tumor Suppressive and Antimetastatic Properties in Radioresistant A549 Non-Small Cell Lung Cancer Cells
1 Institute of Future Biophysics, Dolgoprudny, Russia
2 Department of Molecular Genetics and Microbiology, Institute of Medical Research, Israel–Canada,
Faculty of Medicine, Hebrew University, Jerusalem, Israel
3 A.F. Tsyb Medical Research Center of Radiology, Obninsk, Russia
4 Pushchino Scientific Center for Biological Research Institute of Cell Biophysics, Pushchino, Russia
Contact person: M.V. Pustovalova, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.
ABSTRACT
Purpose: Lung cancer is the leading cause of death worldwide, with non-small cell lung cancer (NSCLC) accounting for 85 % of all lung cancers. Combined chemoradiotherapy is one of options in the treatment of patients with inoperable NSCLC. However, the prognosis of NSCLC remains unsatisfactory due to the development of radio- and chemo-resistance of cancer cells. This study aimed to investigate how the overexpression of miR-16, miR-16-1-3p, and miR-16-2-3p influences clonogenic survival, migration, and sensitivity to cisplatin in both radiosensitive and radioresistant non-small cell lung cancer (NSCLC) cells.
Material and methods: This study involved the application of single proton beam irradiation to A549 NSCLC cells, resulting in the emergence of a subline of resilient radioresistant daughter cells, designated as A549IR. To explore the functional role of the miR-16, miR-16-1-3p, and miR-16-2-3p in NSCLC, we overexpressed the “leader” miR-16 as well as the “passenger” miR-16-1-3p and miR-16-2-3p strands in both the parental A549 and their radioresistant variant, A549IR cells. The impact of microRNA overexpression on cell viability was evaluated through a clonogenic assay. Additionally, cisplatin sensitivity was measured by calculating the total mass of surviving cells via the sulforhodamine B method. Furthermore, the capacity for cell migration and invasion was investigated using Boyden chambers.
Results: Overexpressing miR-16, miR-16-1-3p, and miR-16-2-3p significantly reduced the ability of A549 and radioresistant A549IR NSCLC cells to survive, clone, migrate, and invade, compared to cells with normal levels of these microRNAs. Moreover, the stable overexpression of these microRNAs markedly enhanced the sensitivity of A549 and A549IR cells to the cytotoxic effects of cisplatin, allowing for a nearly threefold reduction in the concentration needed to achieve 50 % cell death.
Conclusion: An increase in the expression of “passenger” miR-16-1-3p and miR-16-2-3p, as well as the “leader” miR-16, exhibits a robust tumor-suppressive and cisplatin-sensitizing activities in both the radiation-sensitive parental and the radiation-resistant daughter cells in the human NSCLC A549 lineage.
Keywords: non-small cell lung cancer, chemo-radiotherapy, radioresistance, metastasis, invasiveness, miR-16, miR-16-1; miR-16-2
For citation: Malakhov PA, Maximov VV, Pustovalova MV, Smirnova AV, Nofal Z, Saburov V, Osipov AN, Kuzmin DV, Leonov SV. MiR-16-1-3p and miR-16-2-3p Overexpression Confers Tumor Suppressive and Antimetastatic Properties in Radioresistant A549 Non-Small Cell Lung Cancer Cells. Medical Radiology and Radiation Safety. 2025;70(2):27–34. (In Russian). DOI:10.33266/1024-6177-2025-70-2-27-34
References
1. Bray F., Laversanne M., Sung H., et al. Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2024;74;3:229-263. doi:10.3322/caac.21834 PMID: 38572751
2. Zhou T., Zhang L.Y., He J.Z., et al. Review: Mechanisms and Perspective Treatment of Radioresistance in Non-Small Cell Lung Cancer. Front Immunol. 2023;14:1133899. Published 2023 Feb 14. doi:10.3389/fimmu.2023.1133899 PMID: 36865554
3. Jonas S., Izaurralde E. Towards a Molecular Understanding of MicroRNA-Mediated Gene Silencing. Nat Rev Genet. 2015;16;7:421-433. doi:10.1038/nrg3965 PMID: 26077373
4. O’Brien J., Hayder H., Zayed Y., Peng C. Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation. Front Endocrinol (Lausanne). 2018;9:402. doi:10.3389/fendo.2018.00402 PMID: 30123182
5. Daugaard I., Hansen T.B. Biogenesis and Function of Ago-Associated RNAs. Trends Genet. 2017;33;3:208-219. doi:10.1016/j.tig.2017.01.003 PMID: 28174021
6. Peng Y., Croce C.M. The Role of MicroRNAs in Human Cancer. Signal Transduct Target Ther. 2016;1:15004. doi:10.1038/sigtrans.2015.4 PMID: 29263891
7. Klein U., Lia M., Crespo M., et al. The DLEU2/miR-15a/16-1 Cluster Controls B Cell Proliferation and its Deletion Leads to Chronic Lymphocytic Leukemia. Cancer Cell. 2010;17;1:28-40. doi:10.1016/j.ccr.2009.11.019 PMID: 20060366
8. Lovat F., Fassan M., Gasparini P., et al. MiR-15b/16-2 Deletion Promotes B-Cell Malignancies. Proc Natl Acad Sci USA. 2015;112;37:11636-11641. doi:10.1073/pnas.1514954112 PMID: 26324892
9. Lovat F., Fassan M., Sacchi D., et al. Knockout of Both miR-15/16 Loci Induces Acute Myeloid Leukemia. Proc Natl Acad Sci USA. 2018;115;51:13069-13074. doi:10.1073/pnas.1814980115 PMID: 30478046
10. Maximov V.V., Akkawi R., Khawaled S., et al. MiR-16-1-3p and MiR-16-2-3p Possess Strong Tumor Suppressive and Antimetastatic Properties in Osteosarcoma. Int J Cancer. 2019;145;11:3052-3063. doi:10.1002/ijc.32368 PMID: 31018244
11. Hu H., Chen C., Chen F., Sun N. LINC00152 Knockdown Suppresses Tumorigenesis in Non-Small Cell Lung Cancer Via Sponging MiR-16-5p. J Thorac Dis. 2022;14;3:614-624. doi:10.21037/jtd-22-59 PMID: 35399229
12. Biton M., Levin A., Slyper M., et al. Epithelial MicroRNAs Regulate Gut Mucosal Immunity Via Epithelium-T Cell Crosstalk. Nat Immunol. 2011;12;3:239-246. doi:10.1038/ni.1994 PMID: 21278735
13. Chava S., Reynolds C.P., Pathania A.S., et al. MiR-15a-5p, MiR-15b-5p, and MiR-16-5p Inhibit Tumor Progression by Directly Targeting MYCN in Neuroblastoma. Mol Oncol. 2020;14;1:180-196. doi:10.1002/1878-0261.12588 PMID: 31637848
14. Calin G.A., Ferracin M., Cimmino A, et al. A MicroRNA Signature Associated with Prognosis and Progression in Chronic Lymphocytic Leukemia [Published Correction Appears in N Engl J Med. 2006 Aug 3;355(5):533]. N Engl J Med. 2005;353;17:1793-1801. doi:10.1056/NEJMoa050995 PMID: 16251535
15. Zhou Y., Huang Y., Dai T., et al. LncRNA TTN-AS1 Intensifies Sorafenib Resistance in Hepatocellular Carcinoma by Sponging MiR-16-5p and Upregulation of Cyclin E1. Biomed Pharmacother. 2021;133:111030. doi:10.1016/j.biopha.2020.111030 PMID: 33378944
16. Zhang X., Zhang J., Liu Q., Zhao Y., Zhang W., Yang H. Circ-CUX1 Accelerates the Progression of Neuroblastoma Via MiR-16-5p/DMRT2 Axis. Neurochem Res. 2020;45;12:2840-2855. doi:10.1007/s11064-020-03132-w PMID: 33000435
17. Wang Z., Hu S., Li X., et al. MiR-16-5p Suppresses Breast Cancer Proliferation by Targeting ANLN. BMC Cancer. 2021;21;1:1188. doi:10.1186/s12885-021-08914-1 PMID: 34743685
18. Du R., Jiang F., Yin Y., et al. Knockdown of lncRNA X Inactive Specific Transcript (XIST) Radiosensitizes Non-Small Cell Lung Cancer (NSCLC) Cells through Regulation of MiR-16-5p/WEE1 G2 Checkpoint Kinase (WEE1) Axis. Int J Immunopathol Pharmacol. 2021;35:2058738420966087. doi:10.1177/2058738420966087 PMID: 33583218
19. Wang Q., Chen Y., Lu H., et al. Quercetin Radiosensitizes Non-Small Cell Lung Cancer Cells through the Regulation of miR-16-5p/WEE1 axis. IUBMB Life. 2020;72;5:1012-1022. doi:10.1002/iub.2242 PMID: 32027086
20. Mohammadi C., Gholamzadeh Khoei S., Fayazi N., Mohammadi Y., Najafi R. MiRNA as Promising Theragnostic Biomarkers for Predicting Radioresistance in Cancer: A Systematic Review and Meta-Analysis. Crit Rev Oncol Hematol. 2021;157:103183. doi:10.1016/j.critrevonc.2020.103183 PMID: 33310279
PDF (RUS) Full-text article (in Russian)
Conflict of interest. The authors declare no conflict of interest.
Financing. The work was supported by Russian Science Foundation (agreement No 23-14-00220).
Contribution. Article was prepared with equal participation of the authors.
Article received: 20.12.2024. Accepted for publication: 25.01.2025.