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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">medinfo</journal-id><journal-title-group><journal-title xml:lang="ru">Актуальные проблемы теоретической и клинической медицины</journal-title><trans-title-group xml:lang="en"><trans-title>Actual Problems of Theoretical and Clinical Medicine</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2790-1289</issn><issn pub-type="epub">2790-1297</issn><publisher><publisher-name>Казахстанско-Российский медицинский университет</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.24412/2790-1289-2023-4-10-19</article-id><article-id custom-type="elpub" pub-id-type="custom">medinfo-372</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL ARTICLES</subject></subj-group></article-categories><title-group><article-title>Мутации генов, ответственных за рост и деление клеток при аденокарциноме и плоскоклеточном раке легкого</article-title><trans-title-group xml:lang="en"><trans-title>Mutations of genes responsible for the growth and division of cells in adenocarcinoma and squamous cell lung cancer</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Ермекова</surname><given-names>С. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Yermekova</surname><given-names>S. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Ермекова Сауле Алихановна, Д.м.н., ассоц.профессор,</p><p>г. Алматы.</p></bio><bio xml:lang="en"><p>Ermekova Saule Alikhanovna, Doctor of Medical Sciences, Professor,</p><p>Almaty.</p></bio><email xlink:type="simple">saule.yermekova@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Жанатаев</surname><given-names>Б. Т.</given-names></name><name name-style="western" xml:lang="en"><surname>Zhanataev</surname><given-names>B. T.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Жанатаев Бауыржан Туралыулы, магистр, старший преподаватель,</p><p>г. Алматы.</p></bio><bio xml:lang="en"><p>Zhanataev Bauyrzhan Turalyuly, Master's degree, Senior Lecturer,</p><p>Almaty.</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Серик</surname><given-names>Е. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Serik</surname><given-names>E. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Серик Эльмира Сериккызы, магистр педагогических наук, старший преподаватель,</p><p>г. Алматы.</p></bio><bio xml:lang="en"><p>Serik Elmire Serikkazy, Master of Pedagogical Sciences, Senior Lecturer,</p><p>Almaty.</p></bio><xref ref-type="aff" rid="aff-2"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru">НУО «Казахстанско-Российский медицинский университет» (КРМУ)<country>Казахстан</country></aff><aff xml:lang="en">Kazakh-Russian Medical University (KRMU)<country>Kazakhstan</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru">Каспийский университет<country>Казахстан</country></aff><aff xml:lang="en">Caspian University<country>Kazakhstan</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2023</year></pub-date><pub-date pub-type="epub"><day>29</day><month>12</month><year>2023</year></pub-date><volume>0</volume><issue>4</issue><fpage>10</fpage><lpage>19</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Ермекова С.А., Жанатаев Б.Т., Серик Е.С., 2023</copyright-statement><copyright-year>2023</copyright-year><copyright-holder xml:lang="ru">Ермекова С.А., Жанатаев Б.Т., Серик Е.С.</copyright-holder><copyright-holder xml:lang="en">Yermekova S.A., Zhanataev B.T., Serik E.S.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://kazrosmedjournal.krmu.edu.kz/jour/article/view/372">https://kazrosmedjournal.krmu.edu.kz/jour/article/view/372</self-uri><abstract><p>P53 (который кодирует белок p53) является одним из наиболее часто мутирующих генов при всех раковых заболеваниях человека. Распространенные миссенс-мутации p53 отменяют его опухоль-подавляющую функцию и приводят к развитию рака GOF.Материалы и методы. Объектом исследования являлись образцы плоскоклеточного рака, аденокарцином легких и прилегающих здоровых тканей, взятые из послеоперационного материалау онкологических больных. Методы включали полимеразную цепную реакцию фрагментов гена p53 и HRAS, а также комплементарных ДНК (c-DNA) копий мРНК p53, p21Waf 1, MDM2 и анализа мутаций с помощью эндонуклеаз EcoR 1 и Pst1 по наличию сайтов рестрикции.Результаты. Анализировали наличие мутаций после амплификации фрагментов генов p53 и HRAS, а также мРНК p53, p21Waf1 и MDM2 в раковых и прилегающих тканях в 100 образцах опухолевых и нормальных прилегающих тканях. Половина образцов плоскоклеточного рака и аденокарциномы легких не содержали продуктов экспрессии генов p53 или p21Waf1. Мутации выявлены в 100 % и 85 % образцов плоскоклеточного рака в 12 и 61 кодонах гена HRAS и в 75 % и 50 % образцов аденокарциномы легких, соответственно.Заключение. Мутации, обнаруженные в большинстве образцов плоскоклеточного рака и аденокарциномы легких, позволяют с помощью таких тестов диагностировать заболевание, прогнозировать его тяжесть и эффективность целевой терапии.</p></abstract><trans-abstract xml:lang="en"><p>P53 (encoding the p53 protein) is one of the most frequently mutated genes in all human cancer diseases. Common missense mutations of p53 abolish its tumor-suppressing function (gain-of-function, GOF)and lead to the development of GOF cancer.Materials and Methods. The study focused on samples of squamous cell carcinoma, adenocarcinoma of the lungs, and adjacent healthy tissues obtained from postoperative material of cancer patients.Methods included polymerase chain reaction of p53 and HRAS gene fragments, as well as complementary DNA (c-DNA) copies of p53, p21Waf1, MDM2, and mutation analysis using EcoR1 and Pst1 endonucleases based on restriction site presence.Results. The presence of mutations was analyzed after amplification of p53 and HRAS gene fragments, as well as p53, p21Waf1, and MDM2 mRNA in cancerous and adjacent tissues in 100 samples of tumor and normal adjacent tissues. Half of the SCC and ADC lung samples did not contain expression products of p53 or p21Waf1 genes. Mutations were detected in 100 % and 85 % of SCC samples in 12 and61 codons of the HRAS gene, and in 75 % and 50 % of ADC samples, respectively.Conclusion. Mutations found in the majority of SCC and ADC samples allow diagnosing the disease, predicting its severity, and assessing the effectiveness of targeted therapy through such tests.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>мутации гена</kwd><kwd>аденокарцинома легких</kwd><kwd>плоскоклеточный рак</kwd><kwd>GOF – приобретение другой функции</kwd><kwd>прилегающая нормальная ткань</kwd></kwd-group><kwd-group xml:lang="en"><kwd>gene mutations</kwd><kwd>lung adenocarcinoma</kwd><kwd>squamous cell carcinoma</kwd><kwd>GOF – gene function change</kwd><kwd>adjacent normal tissue</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Zhu J., Sammons M. A., Donahue G., Dou Z., Vedadi M., Getlik M., Barsyte-Lovejoy D., Alwar R., Katona B. W., Shilatifard A., Huang J., Hua X., Arrowsmith C. H., Berger S. L. Gain-of-function p53 mutants co-opt chromatin pathways to drive cancer growth // Nature. – 2015. – Vol. 525(7568). – P. 206-211. – DOI: 10.15252/embj.201899599.</mixed-citation><mixed-citation xml:lang="en">Zhu, J., Sammons, M. A., Donahue, G., Dou, Z., Vedadi, M., Getlik, M., Barsyte-Lovejoy, D., Al-war, R., Katona, B. W., Shilatifard, A., Huang, J., Hua, X., Arrowsmith, C. H. and Berger, S. L. (2015). Gain-of-function p53 mutants coopt chromatin pathways to drive cancer growth. Nature, 525(7568), 206-211, DOI: 10.15252/embj.201899599.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Ding J., Yu C., Sui Y., Wang L., Yang Y., Wang F., Yao H., Xing F., Liu H., Li Y., Shah J. A., Cai Y., Jin J. The chromatin remodeling protein INO80 contributes to the removal of H2A.Z at the p53binding site of the p21 gene in response to doxorubicin // The FEBS Journal. – 2018. – Vol. 285. – P. 3270-3285. – DOI: 10.1111/febs.14615.</mixed-citation><mixed-citation xml:lang="en">Ding, J., Yu, C., Sui, Y., Wang, L., Yang, Y., Wang, F., Yao, H., Xing, F., Liu, H., Li, Y., Shah, J. A., Cai, Y. and Jin, J. (2018). The chromatin remodeling protein INO80 contributes to the removal of H2A.Z at the p53‐binding site of the p21 gene in response to doxorubicin. The FEBS Journal, 285, 3270-3285, DOI: 10.1111/febs.14615.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Sui Y., Wu T., Li F., Wang F., Cai Y., Jin J. YY1 / BCCIP Coordinately Regulates P53-Responsive Element (p53RE)-Mediated Transactivation of p21 Waf1 / Cip1 // International Journal of Molecular Sciences. – 2019. – Vol. 20(9). – P. 2095. – DOI: 10.3390/ijms20092095.</mixed-citation><mixed-citation xml:lang="en">Sui, Y., Wu, T., Li, F., Wang, F., Cai, Y. and Jin, J. (2019). YY1 / BCCIP Coordinately Regulates P53Responsive Element (p53RE)-Mediated Transactivation of p21 Waf1 / Cip1. International Journal of Molecular Sciences, 20(9), 2095, DOI: 10.3390/ijms20092095.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Meliala ITS., Hosea R., Kasim V., Wu S. The biological implications of Yin Yang 1 in the hallmarks of cancer // Theranostics. – 2020. – Vol. 10(9). – P. 4183-4200. – DOI: 10.7150/thno.43481.</mixed-citation><mixed-citation xml:lang="en">Meliala, ITS., Hosea, R., Kasim, V. and Wu, S. (2020). The biological implications of Yin Yang 1 in the hallmarks of cancer. Theranostics, 10(9), 4183-4200, DOI: 10.7150/thno.43481.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Cao L., Ding J., Dong L., Zhao J., Su J., Wang L., Sui Y., Zhao T., Wang F., Jin J. Negative Regulation of p21Waf1/Cip1 by Human INO80 Chromatin Remodeling Complex Is Implicated in Cell Cycle Phase G2/M Arrest and Abnormal Chromosome Stability // PLoS ONE. – 2015. – Vol. 10(9). – Article no. 0137411. – DOI: 10.1371/journal.pone.0137411.</mixed-citation><mixed-citation xml:lang="en">Cao, L., Ding, J., Dong, L., Zhao, J., Su, J., Wang, L., Sui, Y., Zhao, T., Wang, F. and Jin, J. (2015). Negative Regulation of p21Waf1/Cip1 by Human INO80 Chromatin Remodeling Complex Is Implicated in Cell Cycle Phase G2/M Arrest and Abnormal Chromosome Stability. PLoS ONE, 10(9), 0137411, DOI: 10.1371/journal.pone.0137411.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Khoury K., Domlng A. P53 Mdm2 Inhibitors // Current Pharmaceutical Design. – 2012. – Vol. 18(30). – P. 4668-4678. – DOI: 10.2174/138161212802651580/.</mixed-citation><mixed-citation xml:lang="en">Khoury, K. and Domlng, A. P53 Mdm2 Inhibitors. Current Pharmaceutical Design, 2012, 18(30), 4668-4678, DOI: 10.2174/138161212802651580/.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Estrada-Ortiz N., Neochoritis C. G., Domling A. How to Design a Successful p53-MDM2/X Interaction Inhibitor: A Thorough Overview Based on Crystal Structures // ChemMedChem. – 2016. – Vol. 11(8). – P. 757-772. – DOI: 10.1002/cmdc.201500487.</mixed-citation><mixed-citation xml:lang="en">Estrada-Ortiz, N., Neochoritis, C. G. and Domling, A. (2016). How to Design a Successful p53MDM2/X Interaction Inhibitor: A Thorough Overview Based on Crystal Structures. ChemMedChem, 11(8), 757-772, DOI: 10.1002/cmdc.201500487.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">To M. D., Rosario R. D., Westcott P. M., Banta K. L., Balmain A. Interactions between wild-type and mutant Ras genes in lung and skin carcinogenesis // Oncogene. – 2013. – Vol. 32(34). – P. 40284033. – DOI: 10.1038/onc.2012.404.</mixed-citation><mixed-citation xml:lang="en">To, M. D., Rosario, R. D., Westcott, P. M., Banta, K. L. and Balmain, A. (2013). Interactions between wild-type and mutant Ras genes in lung and skin carcinogenesis. Oncogene, 32(34), 4028-4033, DOI: 10.1038/onc.2012.404.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Asfar S. Conquering RAS, 1st ed. Academic Press. – 2016. – 297 p.</mixed-citation><mixed-citation xml:lang="en">Asfar, S. (2016). Conquering RAS, 1st ed. Academic Press, 297 p.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Mehta A., Dalle Vedove E., Isert L., Merkel O. M. Targeting KRAS Mutant Lung Cancer Cells with siRNA-Loaded Bovine Serum Albumin Nanoparticles // Pharmaceutical Research. – 2019. – Vol. 36(9). – P. 133. – DOI: 10.1007/s11095-0192665-9.</mixed-citation><mixed-citation xml:lang="en">Mehta, A., Dalle Vedove, E., Isert, L. and Merkel, O. M. (2019). Targeting KRAS Mutant Lung Cancer Cells with siRNA-Loaded Bovine Serum Albumin Nanoparticles. Pharmaceutical Research, 36(9), 133, DOI: 10.1007/s11095-0192665-9.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Naghizadeh S., Mohammadi A., Baradaran B., Mansoori B. Overcoming multiple drug resistance in lung cancer using siRNA targeted therapy // Gene. – 2019. – Vol. 714. – Article no. 143972. – DOI: 10.1016/j.gene.2019.143972.</mixed-citation><mixed-citation xml:lang="en">Naghizadeh, S., Mohammadi, A., Baradaran, B. and Mansoori, B. (2019). Overcoming multiple drug resistance in lung cancer using siRNA targeted therapy. Gene, 714, 143972, DOI: 10.1016/j.gene.2019.143972.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Singh S. S., Dahal A., Shrestha L., Jois S. D. Genotype driven therapy for non-small cell lung cancer: resistance, pan inhibitors and immunotherapy // Current Medical Chemistry. – 2020. – Vol. 27. – P. 5274. – DOI: 10.2174/0929867326666190222183219.</mixed-citation><mixed-citation xml:lang="en">Singh, S. S., Dahal, A., Shrestha, L. and Jois, S. D. (2020). Genotype driven therapy for non-small cell lung cancer: resistance, pan inhibitors and immunotherapy. Current Medical Chemistry, 27, 5274, DOI: 10.2174/0929867326666190222183219.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Hay N., Sonenberg N. Upstream and downstream of mTOR // Genes &amp; Development. – 2004. – Vol. 18. – P. 1926-1945. – DOI: 10.1101/gad.1212704.</mixed-citation><mixed-citation xml:lang="en">Hay, N. and Sonenberg, N. (2004). Upstream and downstream of mTOR. Genes &amp; Development, 18, 1926-1945, DOI: 10.1101/gad.1212704.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Beevers C. S., Li F., Liu L., Huang S. Curcumin inhibits the mammalian target of rapamycin-mediated signaling pathways in cancer cells // International Journal of Cancer. – 2006. – Vol. 119. – P. 757-764. – DOI: 10.1002/ijc.21932.</mixed-citation><mixed-citation xml:lang="en">Beevers, C. S., Li, F., Liu, L. and Huang, S. (2006). Curcumin inhibits the mammalian target of rapamycin-mediated signaling pathways in cancer cells. International Journal of Cancer, 119, 757764, DOI: 10.1002/ijc.21932.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Liu X., Zhang X., Meng J., Zhang H., Zhao Y., Li C., Sun Y., Mei Q., Zhang F., Zhang T. ING5 knockdown enhances migration and invasion of lung cancer cells by inducing EMT via EGFR/ PI3K/Akt and IL-6/STAT3 signaling pathways // Oncotarget. – 2017. – Vol. 8. – P. 54265-54276. – DOI: 10.18632/oncotarget.17346.</mixed-citation><mixed-citation xml:lang="en">Liu, X., Zhang, X., Meng, J., Zhang, H., Zhao, Y., Li, C., Sun, Y., Mei, Q., Zhang, F. and Zhang, T. (2017). ING5 knockdown enhances migration and invasion of lung cancer cells by inducing EMT via EGFR/PI3K/Akt and IL-6/STAT3 signaling pathways. Oncotarget, 8, 54265-54276, DOI: 10.18632/oncotarget.17346.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Kawano O., Sasaki H., Endo K., Suzuki E., Haneda H., Yukiue H., Kobayashi Y., Yano M., Fujii Y. PIK3CA mutation status in Japanese lung cancer patients // Lung Cancer. – 2006. – Vol. 54. – P. 209-215. – DOI: 10.1016/j.lungcan.2006.07.006.</mixed-citation><mixed-citation xml:lang="en">Kawano, O., Sasaki, H., Endo, K., Suzuki, E., Haneda, H., Yukiue, H., Kobayashi, Y., Yano, M. and Fujii, Y. (2006). PIK3CA mutation status in Japanese lung cancer patients. Lung Cancer, 54, 209-215, DOI: 10.1016/j.lungcan.2006.07.006.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
