Экспрессия генов DROSHA и DICER в лейкоцитах периферической крови при саркоидозе легких
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Материалы и методы. В исследование включено 32 пациента с диагнозом персистирующий саркоидоз легких (средний возраст 41,56±1,27 года) и 36 здоровых доноров (контроль; средний возраст 42,79±1,95 года). Уровень экспрессии матричной РНК (мРНК) генов DROSHA и DICER определяли в ЛПК здоровых доноров и больных саркоидозом легких методом полимеразной цепной реакции в режиме реального времени.
Результаты. Установлено, что уровень экспрессии гена DROSHA в ЛПК больных саркоидозом легких значимо снижен по сравнению с контролем (р<0,01). Нами также обнаружено достоверное снижение количества транскриптов гена DICER в ЛПК исследуемой группы больных (р<0,01).
Заключение. Установлено значимое снижение количества транскриптов генов DROSHA и DICER в ЛПК больных при развитии саркоидоза легких, что может вносить определенный вклад в патогенез данного заболевания.
Ключевые слова: саркоидоз легких, микроРНК, биогенез микроРНК, гены DROSHA и DICER, экспрессия.
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Aim. To study the expression level of the genes DROSHA and DICER in peripheral blood leukocytes (PBL) of patients with sarcoidosis of the lungs
Materials and methods. The study included 32 patients diagnosed with persistent lung sarcoidosis (mean age 41.56±1.27 years) and 36 healthy donors (control; mean age 42.79±1.95 years). The level of expression of messenger RNA (mRNA) of the genes DROSHA and DICER were determined in PBL of healthy donors and patients with sarcoidosis of the lung by polymerase chain reaction in real time.
Results. As a result of the conducted researches it is established that the level of drosha gene expression in PBL patients with sarcoidosis of lungs is significantly reduced in comparison with the control (p<0.01). We also found a significant decrease in the number of Dicker gene transcripts in the PBL of the study group of patients (p<0.01).
Conclusion. According to the results of the conducted studies, a significant decrease in the number of DROSHA and DICER transcripts in PBL patients with the development of lung sarcoidosis has been found, which can contribute to the pathogenesis of this disease.
Keywords: sarcoidosis of the lung, microRNA, microRNA biogenesis, DICER and DROSHA genes expression.
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4. Iannuzzi M, Rybicki B, Teirstein A. Sarcoidosis. The New England journal of medicine. 2007; 357: 2153-2165. doi: 10.1056/NEJMra071714
5. Lazarus A. Sarcoidosis: epidemiology, etiology, pathogenesis, and genetics. Disease-a-month: DM. 2009; 55: 649-660. doi: 10.1016/j.disamonth.2009.04.008
6. Spagnolo P, Grunewald J. Recent advances in the genetics of sarcoidosis. Journal of medical genetics. 2013; 50: 290-297. doi: 10.1136/jmedgenet-2013-101532.
7. Tzouvelekis A, Ntolios Tzouvelekis A, Ntolios P, Karameris A, Koutsopoulos A, Boglou P, Koulelidis A, Archontogeorgis K, Zacharis G, Drakopanagiotakis F, Steiropoulos P, Anevlavis S, Polychronopoulos V, Mikroulis D, Bouros D. Expression of hypoxia-inducible factor (HIF)-1a-vascular endothelial growth factor (VEGF)-inhibitory growth factor (ING)-4- axis in sarcoidosis patients. BMC research notes. 2012; 5: 654. doi: 10.1186/1756-0500-5-654
8. Wu F, Yang Z, Li G. Role of specific microRNAs for endothelial function and angiogenesis. Biochemical and biophysical research communications. 2009; 386: 549-53. doi: 10.1016/j.bbrc.2009.06.075
9. Magner W, Weinstock-Guttman B, Rho M, Hojnacki D, Ghazi R, Ramanathan M, Tomasi T. Dicer and microRNA expression in multiple sclerosis and response to interferon therapy. Journal of neuroimmunology. 2016; 292: 68-78. doi: 10.1016/j.jneuroim.2016.01.009
10. Saeki M, Watanabe M, Inoue N, Tokiyoshi E, Takuse Y, Arakawa Y, Hidaka Y, Iwatani Y. DICER and DROSHA gene expression and polymorphisms in autoimmune thyroid diseases. Autoimmunity. 2016; 49 (8): 514-522. doi: 10.1080/08916934.2016.1230846
11. Kiszałkiewicz J, Piotrowski W, Pastuszak-Lewandoska D, Górski P, Antczak A, Górski W, Domańska-Senderowska D, Migdalska-Sęk M, Czarnecka KH, Nawrot E, Brzeziańska-Lasota E. Altered miRNA expression in pulmonary sarcoidosis. BMC medical genetics. 2016; 17: 2. doi: 10.1186/s12881-016-0266-6
12. Jazwa A, Kasper L, Bak M, Sobczak M, Szade K, Jozkowicz A, Sladek K, Dulak J. Differential nflammatory microRNA and cytokine expression in pulmonary sarcoidosis. Archivum immunologiae et therapiae experimentalis. 2015; 63 (2): 139-146. doi: 10.1007/s00005-014-0315-9
13. [Baulina NM, Kulakova OG, Favorova OО. MicroRNAs: role in the development of autoimmune inflammation. Acta Naturae. 2016; 8 (1): 23-35. (In Russ.)]. http://elibrary.ru/item.asp?id=25790907
14. Bartel D. MicroRNAs: target recognition and regulatory functions. Cell. 2009; 136; 215–233. doi: 10.1016/j.cell.2009.01.002
15. [Fedorov AV, Kostareva AA. Modern methods of modulation and visualization of endogenous microRNAs. Bulletin of the Federal center of heart, blood and endocrinology them. V. A. Almazov. 2012; (5): 77-81. (In Russ.)] http://elibrary.ru/item.asp? id= 18828562
16. Kim S, Lee J, Nam S. Dicer Is Down-regulated and Correlated with Drosha in Idiopathic Sudden Sensorineural Hearing Loss. Journal of Korean medical sciencei. 2015; 30 (8): 1183-1188. doi: 10.3346/jkms. 2015.30.8.1183
17. Jackson RJ, Standart N. How do microRNAs regulate gene expression? Science's signal transduction knowledge environment. 2007; (367): re1. doi: 10.1126/stke.3672007re1
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19. Guo X, Liao Q, Chen P, Li X, Xiong W, Ma J, Li X, Luo Z, Tang H, Deng M, Zheng Y, Wang R, Zhang W, Li G. The microRNA-processing enzymes: Drosha and Dicer can predict prognosis of nasopharyngeal carcinoma. Journal of cancer research and clinical oncology. 2012; 138 (1): 49-56. doi: 10.1007/s00432-011-1058-1
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21. Dyskova T, Fillerova R, Novosad T,Kudelka M, Zurkova M, Gajdos P2, Kolek V, Kriegova E. Correlation Network Analysis Reveals Relationships between MicroRNAs, Transcription Factor T-bet, and Deregulated Cytokine/Chemokine-Receptor Network in Pulmonary Sarcoidosis. Mediators of inflammation. 2015: 121378. doi: 10.1155/2015/ 121378
22. Alsaleh G, Nehmar R, Blüml S, Schleiss C, Ostermann E, Dillenseger J, Sayeh A, Choquet P, Dembele D, Francois A, Salmon J, Paul N, Schabbauer G, Bierry G, Meyer A, Gottenberg J, Haas G, Pfeffer S, Vallat L, Sibilia J, Bahram S, Georgel P. Reduced DICER1 Expression Bestows Rheumatoid Arthritis Synoviocytes Proinflammatory Properties and Resistance to Apoptotic Stimuli. Arthritis & rheumatology (Hoboken NJ). 2016; 68 (8): 1839-1848. doi: 10.1002/art.39641
23. Rostami Mogaddam M, Safavi Ardabili N, Shafaeei Y, Maleki N, Jafari N5, Jafari A. Overexpression of Drosha, DiGeorge syndrome criticalnregion gene 8 (DGCR8), and Dicer mRNAs in the pathogenesis of psoriasis. Journal of cosmetic dermatology. 2017. doi: 10.1111/jocd. 12336. [Epub ahead of print]
24. Valeyre D, Prasse A, Nunes H, Uzunhan Y, Brillet P, Müller-Quernheim J. Sarcoidosis. Lancet. 2014; 383 (9923): 1155-1167. doi: 10.1016/S0140-6736(13)60680-7
25. Zissel G, Müller-Quernheim J. Specific antigen(s) in sarcoidosis: a link to autoimmunity? The European respiratory journal. 2016; 47 (3): 707-709. doi: 10.1183/13993003.01791-2015.
1 ФГБУ Институт биологии Карельского научного центра РАН, Петрозаводск, Россия;
2 Республиканская больница им. В.А. Баранова, Петрозаводск, Россия;
3 ФГБУ ВО «Петрозаводский государственный университет», Петрозаводск, Россия
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I.E. MALYSHEVA 1, O.V. BALAN 1, E.L. TIKHONOVICH 2, T.O. VOLKOVA 3
1 IB KarRC RAS, laboratory of genetics, Petrozavodsk, Russia;
2 Republican Hospital named after. V.A. Baranov, Petrozavodsk, Russia;
3 Petrozavodsk state University, Department of Hospital Therapy, Petrozavodsk, Russia