Экспрессия генов DICER и DROSHA в лейкоцитах периферической крови больных ревматоидным артритом на фоне терапии метотрексатом - Журнал Терапевтический архив № 5 Вопросы ревматологии 2018
Экспрессия генов DICER и DROSHA в лейкоцитах периферической крови больных ревматоидным артритом на фоне терапии метотрексатом
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Аннотация
Цель исследования – изучить уровень экспрессии генов DICER и DROSHA в лейкоцитах периферической крови (ЛПК) больных ревматоидным артритом (РА) на фоне терапии метотрексатом.
Материалы и методы. В исследование включено 82 человека (в возрасте от 45 до 70 лет), которых разделили на 3 группы: I – контроль (здоровые доноры; n=33, средний возраст 49,93 ±1,87 года), II – больные РА в дебюте заболевания (n=15, средний возраст 57,28±15,18 года) и III – больные РА, которые получали не менее 4 нед базисную терапию метотрексатом в дозе 10–20 мг/нед (n=34, средний возраст 60,88±9,02 года). Уровень экспрессии генов DICER и DROSHA определяли в ЛПК здоровых доноров, больных РА в дебюте заболевания и на фоне терапии метотрексатом методом полимеразной цепной реакции в режиме реального времени.
Результаты. Количество транскриптов гена DICER в лейкоцитах крови больных РА в дебюте заболевания оказалось снижено по сравнению с контролем (р<0,001) и значимо не изменялось на фоне проводимой терапии метотрексатом (р>0,05). Уровень экспрессии мРНК гена DROSHA в лейкоцитах крови достоверно не различался во всех исследуемых группах (р>0,05).
Заключение. Результаты наших исследований показали, что уровень транскриптов гена DICER в ЛПК снижается при развитии РА. Метотрексат не оказывает влияния на содержание мРНК указанного гена в ЛПК.
Ключевые слова: ревматоидный артрит, метотрексат, микроРНК, гены DROSHA и DICER, экспрессия.
Materials and methods. 82 people (from 45 to 70 years) enrolled in this study were divided into 3 groups (the first one – healthy donors (n=33 median age 49.93±1.87); the second group – rheumatoid arthritis patients without any therapy (n=15; median age 57.28±15.18) and the third group (n=34; median age 60.88±9.02) – rheumatoid arthritis patients who treated at least 4 weeks with methotrexate therapy (10-20 mg/week). The DICER and DROSHA genes expression level was determined by real-time PCR.
Results. The number of DICER gene transcripts in PBMC in rheumatoid arthritis patients without therapy as in RA patients treated with methotrexate was reduced in comparison with the healthy donors (p<0.001 and p>0.05 respectively). The level of DROSHA gene expression in PBMC was not significantly different in all groups enrolled in this study (p>0.05).
Conclusion. Our findings suggest that that the DICER gene expression level in perifheral mononuclear blood cells decreased with the development of rheumatoid arthritis. Methotrexate doesn’t influence on the mRNA level of this gene.
Keywords: rheumatoid arthritis, methotrexate, microRNA, DROSHA and DICER genes, expression.
Материалы и методы. В исследование включено 82 человека (в возрасте от 45 до 70 лет), которых разделили на 3 группы: I – контроль (здоровые доноры; n=33, средний возраст 49,93 ±1,87 года), II – больные РА в дебюте заболевания (n=15, средний возраст 57,28±15,18 года) и III – больные РА, которые получали не менее 4 нед базисную терапию метотрексатом в дозе 10–20 мг/нед (n=34, средний возраст 60,88±9,02 года). Уровень экспрессии генов DICER и DROSHA определяли в ЛПК здоровых доноров, больных РА в дебюте заболевания и на фоне терапии метотрексатом методом полимеразной цепной реакции в режиме реального времени.
Результаты. Количество транскриптов гена DICER в лейкоцитах крови больных РА в дебюте заболевания оказалось снижено по сравнению с контролем (р<0,001) и значимо не изменялось на фоне проводимой терапии метотрексатом (р>0,05). Уровень экспрессии мРНК гена DROSHA в лейкоцитах крови достоверно не различался во всех исследуемых группах (р>0,05).
Заключение. Результаты наших исследований показали, что уровень транскриптов гена DICER в ЛПК снижается при развитии РА. Метотрексат не оказывает влияния на содержание мРНК указанного гена в ЛПК.
Ключевые слова: ревматоидный артрит, метотрексат, микроРНК, гены DROSHA и DICER, экспрессия.
________________________________________________
Materials and methods. 82 people (from 45 to 70 years) enrolled in this study were divided into 3 groups (the first one – healthy donors (n=33 median age 49.93±1.87); the second group – rheumatoid arthritis patients without any therapy (n=15; median age 57.28±15.18) and the third group (n=34; median age 60.88±9.02) – rheumatoid arthritis patients who treated at least 4 weeks with methotrexate therapy (10-20 mg/week). The DICER and DROSHA genes expression level was determined by real-time PCR.
Results. The number of DICER gene transcripts in PBMC in rheumatoid arthritis patients without therapy as in RA patients treated with methotrexate was reduced in comparison with the healthy donors (p<0.001 and p>0.05 respectively). The level of DROSHA gene expression in PBMC was not significantly different in all groups enrolled in this study (p>0.05).
Conclusion. Our findings suggest that that the DICER gene expression level in perifheral mononuclear blood cells decreased with the development of rheumatoid arthritis. Methotrexate doesn’t influence on the mRNA level of this gene.
Keywords: rheumatoid arthritis, methotrexate, microRNA, DROSHA and DICER genes, expression.
Список литературы
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2. Ceribelli A, Nahid M, Satoh M, Chan E. MicroRNAs in rheumatoid arthritis. FEBS letters. 2011; 585(23):3667-3674. doi: 10.1016/j.febslet.2011.05.020
3. Баулина Н.М., Кулакова О.Г., Фаворова О.О. МикроРНК: роль в развитии аутоиммунного воспаления. Acta Naturae. 2016; 8(1): 23-35. [Baulina NM, Kulakova OG, Favorova OO. MikroRNK: rol' v razvitii autoimmunnogo vospaleniya. Acta Naturae. 2016; 8(1): 23-35. (In Russ.)]. http://elibrary.ru/item.asp?id=25790907
4. Насонов Е.Л. Проблемы ревматоидного артрита в ХХI столетии. Вестник Российской академии наук. 2015;85(8): 744-754. [Nasonov EL. Problemy revmatoidnogo artrita v XXI stoletii. Vestnik Rossiiskoi akademii nauk. 2015; 85(8): 744-754. (In Russ.)]. doi: https://doi.org/10.7868/s0869587315080204
5. Wittmann J, Jäck H. MicroRNAs in rheumatoid arthritis: midget RNAs with a giant impact. Annals of the rheumatic diseases. 2011; 70:92-96. doi: 10.1136/ard.2010.140152
6. 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
7. 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
8. Nakamachi Y, Kawano S, Takenokuchi M, Nishimura K, Sakai Y, Chin T, Saura R, Kurosaka M, Kumagai S. MicroRNA-124a is a key regulator of proliferation and monocyte chemoattractant protein 1 secretion in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis and rheumatism. 2009; 60:1294-1304. doi:10.1002/art.24475
9. Hruskova V, Jandova R, Vernerova L, Mann H, Pecha O, Prajzlerova K, Pavelka K, Vencovsky J, Filkova M, Senolt L. MicroRNA-125b: association with disease activity and the treatment response of patients with early rheumatoid arthritis. Arthritis research & therapy. 2016; 18(1):124. doi: 10.1186/s13075-016-1023-0
10. Stanczyk J, Ospelt C, Karouzakis E, Filer A, Raza K, Kolling C, Gay R, Buckley C, Tak P, Gay S, Kyburz D. Altered expression of microRNA-203 in rheumatoid arthritis synovial fibroblasts and its role in fibroblast activation. Arthritis and rheumatism. 2011; 63:373-381. doi:10.1002/art.30115
11. Nakasa T, Miyaki S, Okubo A, Hashimoto M, Nishida K, Ochi M, Asahara H. Expression of microRNA-146 in rheumatoid arthritis synovial tissue. Arthritis and rheumatism. 2008; 58:1284-1292. doi:10.1002/ art.23429
12. Pauley K, Satoh M, Chan A, Bubb M, Reeves W, Chan E. Upregulated miR-146a expression in peripheral blood mononuclearncells from rheumatoid arthritis patients. Arthritis research & therapy. 2008; 10(4):R101. doi: 10.1186/ar2493
13. 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
14. 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
15. Aggarwal B. Tumour necrosis factors receptor associated signaling molecules and their role in activation of apoptosis, JNK and NF-kappaB. Ann Rheum Dis. 2000; 59:6-16. doi:10.1136/ard.59.suppl_1.i6
16. Guan Y, Yao H, Wang J, Sun K, Cao L, Wang Y. NF-κB-DICER-miRs Axis Regulates TNF-α Expression in Responses to Endotoxin Stress. International journal of biological sciences. 2015; 11(11):1257-1268. doi: 10.7150/ijbs.12611
17. Малышева И.Е., Топчиева Л.В., Барышева О.Ю., Курбатова И.В., Васькова О.А., Везикова Н.Н., Марусенко И.М., член-корр. РАН Немова Н.Н. Содержание цитокинов и уровень экспрессии генов каспаз при ревматоидном артрите. Доклады Академии наук. 2016; 468(6):707-709. [Malysheva IE, Topchieva LV, Barysheva OYu, Kurbatova IV, Vas'kova OA, Vezikova NN, Marusenko IM, chlen-korrespondent RAN Nemova NN. Soderzhanie tsitokinov i uroven' ekspressii genov kaspaz pri revmatoidnom artrite. Doklady Akademii Nauk. 2016; 468(6):707-709. (In Russ.)]. doi: 10.7868/S0869565216180262
18. Andersson M, Turkkila M, Erlandsson M, Bossios A, Silfverswärd S, Hu D, Ekerljung L, Malmhäll C, Weiner H, Lundbäck B, Bokarewa M. Survivin controls biogenesis of microRNA in smokers: A link to pathogenesis of rheumatoid arthritis. Biochimica et biophysica acta. 2016; 1863(3):663-673. doi:10.1016/j.bbadis.2016.11.033
19. Spurlock C, Gass H, Bryant C, Wells B, Olsen N, Aune T. Methotrexate-mediated inhibition of nuclear factor κB activation by distinct pathways in T cells and fibroblast-like synoviocytes. Rheumatology (Oxford, England). 2015; 54(1):178-187. doi: 10.1093/rheumatology/keu279
20. Kim S, Lee J, Nam S. Dicer Is Down-regulated and Correlated with Drosha in Idiopathic Sudden Sensorineural Hearing Loss. Journal of Korean medical science. 2015; 30(8):1183-1188. doi: 10.3346/jkms. 2015.30.8.1183
2. Ceribelli A, Nahid M, Satoh M, Chan E. MicroRNAs in rheumatoid arthritis. FEBS letters. 2011; 585(23):3667-3674. doi: 10.1016/j.febslet.2011.05.020
3. [Baulina NM, Kulakova OG, Favorova OO. MikroRNK: rol' v razvitii autoimmunnogo vospaleniya. Acta Naturae. 2016; 8(1): 23-35. (In Russ.)]. http://elibrary.ru/item.asp?id=25790907
4. [Nasonov EL. Problemy revmatoidnogo artrita v XXI stoletii. Vestnik Rossiiskoi akademii nauk. 2015; 85(8): 744-754. (In Russ.)]. doi: https://doi.org/10.7868/s0869587315080204
5. Wittmann J, Jäck H. MicroRNAs in rheumatoid arthritis: midget RNAs with a giant impact. Annals of the rheumatic diseases. 2011; 70:92-96. doi: 10.1136/ard.2010.140152
6. 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
7. 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
8. Nakamachi Y, Kawano S, Takenokuchi M, Nishimura K, Sakai Y, Chin T, Saura R, Kurosaka M, Kumagai S. MicroRNA-124a is a key regulator of proliferation and monocyte chemoattractant protein 1 secretion in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis and rheumatism. 2009; 60:1294-1304. doi:10.1002/art.24475
9. Hruskova V, Jandova R, Vernerova L, Mann H, Pecha O, Prajzlerova K, Pavelka K, Vencovsky J, Filkova M, Senolt L. MicroRNA-125b: association with disease activity and the treatment response of patients with early rheumatoid arthritis. Arthritis research & therapy. 2016; 18(1):124. doi: 10.1186/s13075-016-1023-0
10. Stanczyk J, Ospelt C, Karouzakis E, Filer A, Raza K, Kolling C, Gay R, Buckley C, Tak P, Gay S, Kyburz D. Altered expression of microRNA-203 in rheumatoid arthritis synovial fibroblasts and its role in fibroblast activation. Arthritis and rheumatism. 2011; 63:373-381. doi:10.1002/art.30115
11. Nakasa T, Miyaki S, Okubo A, Hashimoto M, Nishida K, Ochi M, Asahara H. Expression of microRNA-146 in rheumatoid arthritis synovial tissue. Arthritis and rheumatism. 2008; 58:1284-1292. doi:10.1002/ art.23429
12. Pauley K, Satoh M, Chan A, Bubb M, Reeves W, Chan E. Upregulated miR-146a expression in peripheral blood mononuclearncells from rheumatoid arthritis patients. Arthritis research & therapy. 2008; 10(4):R101. doi: 10.1186/ar2493
13. 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
14. 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
15. Aggarwal B. Tumour necrosis factors receptor associated signaling molecules and their role in activation of apoptosis, JNK and NF-kappaB. Ann Rheum Dis. 2000; 59:6-16. doi:10.1136/ard.59.suppl_1.i6
16. Guan Y, Yao H, Wang J, Sun K, Cao L, Wang Y. NF-κB-DICER-miRs Axis Regulates TNF-α Expression in Responses to Endotoxin Stress. International journal of biological sciences. 2015; 11(11):1257-1268. doi: 10.7150/ijbs.12611
17. [Malysheva IE, Topchieva LV, Barysheva OYu, Kurbatova IV, Vas'kova OA, Vezikova NN, Marusenko IM, chlen-korrespondent RAN Nemova NN. Soderzhanie tsitokinov i uroven' ekspressii genov kaspaz pri revmatoidnom artrite. Doklady Akademii Nauk. 2016; 468(6):707-709. (In Russ.)]. doi: 10.7868/S0869565216180262
18. Andersson M, Turkkila M, Erlandsson M, Bossios A, Silfverswärd S, Hu D, Ekerljung L, Malmhäll C, Weiner H, Lundbäck B, Bokarewa M. Survivin controls biogenesis of microRNA in smokers: A link to pathogenesis of rheumatoid arthritis. Biochimica et biophysica acta. 2016; 1863(3):663-673. doi:10.1016/j.bbadis.2016.11.033
19. Spurlock C, Gass H, Bryant C, Wells B, Olsen N, Aune T. Methotrexate-mediated inhibition of nuclear factor κB activation by distinct pathways in T cells and fibroblast-like synoviocytes. Rheumatology (Oxford, England). 2015; 54(1):178-187. doi: 10.1093/rheumatology/keu279
20. Kim S, Lee J, Nam S. Dicer Is Down-regulated and Correlated with Drosha in Idiopathic Sudden Sensorineural Hearing Loss. Journal of Korean medical science. 2015; 30(8):1183-1188. doi: 10.3346/jkms. 2015.30.8.1183
2. Ceribelli A, Nahid M, Satoh M, Chan E. MicroRNAs in rheumatoid arthritis. FEBS letters. 2011; 585(23):3667-3674. doi: 10.1016/j.febslet.2011.05.020
3. Баулина Н.М., Кулакова О.Г., Фаворова О.О. МикроРНК: роль в развитии аутоиммунного воспаления. Acta Naturae. 2016; 8(1): 23-35. [Baulina NM, Kulakova OG, Favorova OO. MikroRNK: rol' v razvitii autoimmunnogo vospaleniya. Acta Naturae. 2016; 8(1): 23-35. (In Russ.)]. http://elibrary.ru/item.asp?id=25790907
4. Насонов Е.Л. Проблемы ревматоидного артрита в ХХI столетии. Вестник Российской академии наук. 2015;85(8): 744-754. [Nasonov EL. Problemy revmatoidnogo artrita v XXI stoletii. Vestnik Rossiiskoi akademii nauk. 2015; 85(8): 744-754. (In Russ.)]. doi: https://doi.org/10.7868/s0869587315080204
5. Wittmann J, Jäck H. MicroRNAs in rheumatoid arthritis: midget RNAs with a giant impact. Annals of the rheumatic diseases. 2011; 70:92-96. doi: 10.1136/ard.2010.140152
6. 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
7. 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
8. Nakamachi Y, Kawano S, Takenokuchi M, Nishimura K, Sakai Y, Chin T, Saura R, Kurosaka M, Kumagai S. MicroRNA-124a is a key regulator of proliferation and monocyte chemoattractant protein 1 secretion in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis and rheumatism. 2009; 60:1294-1304. doi:10.1002/art.24475
9. Hruskova V, Jandova R, Vernerova L, Mann H, Pecha O, Prajzlerova K, Pavelka K, Vencovsky J, Filkova M, Senolt L. MicroRNA-125b: association with disease activity and the treatment response of patients with early rheumatoid arthritis. Arthritis research & therapy. 2016; 18(1):124. doi: 10.1186/s13075-016-1023-0
10. Stanczyk J, Ospelt C, Karouzakis E, Filer A, Raza K, Kolling C, Gay R, Buckley C, Tak P, Gay S, Kyburz D. Altered expression of microRNA-203 in rheumatoid arthritis synovial fibroblasts and its role in fibroblast activation. Arthritis and rheumatism. 2011; 63:373-381. doi:10.1002/art.30115
11. Nakasa T, Miyaki S, Okubo A, Hashimoto M, Nishida K, Ochi M, Asahara H. Expression of microRNA-146 in rheumatoid arthritis synovial tissue. Arthritis and rheumatism. 2008; 58:1284-1292. doi:10.1002/ art.23429
12. Pauley K, Satoh M, Chan A, Bubb M, Reeves W, Chan E. Upregulated miR-146a expression in peripheral blood mononuclearncells from rheumatoid arthritis patients. Arthritis research & therapy. 2008; 10(4):R101. doi: 10.1186/ar2493
13. 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
14. 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
15. Aggarwal B. Tumour necrosis factors receptor associated signaling molecules and their role in activation of apoptosis, JNK and NF-kappaB. Ann Rheum Dis. 2000; 59:6-16. doi:10.1136/ard.59.suppl_1.i6
16. Guan Y, Yao H, Wang J, Sun K, Cao L, Wang Y. NF-κB-DICER-miRs Axis Regulates TNF-α Expression in Responses to Endotoxin Stress. International journal of biological sciences. 2015; 11(11):1257-1268. doi: 10.7150/ijbs.12611
17. Малышева И.Е., Топчиева Л.В., Барышева О.Ю., Курбатова И.В., Васькова О.А., Везикова Н.Н., Марусенко И.М., член-корр. РАН Немова Н.Н. Содержание цитокинов и уровень экспрессии генов каспаз при ревматоидном артрите. Доклады Академии наук. 2016; 468(6):707-709. [Malysheva IE, Topchieva LV, Barysheva OYu, Kurbatova IV, Vas'kova OA, Vezikova NN, Marusenko IM, chlen-korrespondent RAN Nemova NN. Soderzhanie tsitokinov i uroven' ekspressii genov kaspaz pri revmatoidnom artrite. Doklady Akademii Nauk. 2016; 468(6):707-709. (In Russ.)]. doi: 10.7868/S0869565216180262
18. Andersson M, Turkkila M, Erlandsson M, Bossios A, Silfverswärd S, Hu D, Ekerljung L, Malmhäll C, Weiner H, Lundbäck B, Bokarewa M. Survivin controls biogenesis of microRNA in smokers: A link to pathogenesis of rheumatoid arthritis. Biochimica et biophysica acta. 2016; 1863(3):663-673. doi:10.1016/j.bbadis.2016.11.033
19. Spurlock C, Gass H, Bryant C, Wells B, Olsen N, Aune T. Methotrexate-mediated inhibition of nuclear factor κB activation by distinct pathways in T cells and fibroblast-like synoviocytes. Rheumatology (Oxford, England). 2015; 54(1):178-187. doi: 10.1093/rheumatology/keu279
20. Kim S, Lee J, Nam S. Dicer Is Down-regulated and Correlated with Drosha in Idiopathic Sudden Sensorineural Hearing Loss. Journal of Korean medical science. 2015; 30(8):1183-1188. doi: 10.3346/jkms. 2015.30.8.1183
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Авторы
И.Е. Малышева 1, Л.В. ТОПЧИЕВА 1, О.В. БАЛАН 1, И.М. МАРУСЕНКО 2, О.Ю. БАРЫШЕВА 2
1 Институт биологии, ФИЦ «Карельский научный центр РАН», лаборатория генетики, Петрозаводск, Россия;
2 Федеральное государственное образовательное учреждение высшего образования «Петрозаводский государственный университет», кафедра госпитальной терапии, Петрозаводск, Россия
1 Institute of Biology of the Karelian Research Centre of the Russian Academy of Sciences, laboratory of genetics; Petrozavodsk, Russia;
2 Federal State Budgetary Educational Institution of Higher Education «Petrozavodsk State University»; Department of Hospital Therapy,
Petrozavodsk, Russia
1 Институт биологии, ФИЦ «Карельский научный центр РАН», лаборатория генетики, Петрозаводск, Россия;
2 Федеральное государственное образовательное учреждение высшего образования «Петрозаводский государственный университет», кафедра госпитальной терапии, Петрозаводск, Россия
________________________________________________
1 Institute of Biology of the Karelian Research Centre of the Russian Academy of Sciences, laboratory of genetics; Petrozavodsk, Russia;
2 Federal State Budgetary Educational Institution of Higher Education «Petrozavodsk State University»; Department of Hospital Therapy,
Petrozavodsk, Russia
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