Volume 6, Issue 4 (12-2018)
Jorjani Biomed J 2018, 6(4): 8-18 |
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Amini Khorasgani M, Mohammady Nejad P, Moghani Bashi M M. Increased Expression of miR-202-3p in Patients with Relapsing-Remitting Multiple Sclerosis. Jorjani Biomed J 2018; 6 (4) :8-18
URL: http://goums.ac.ir/jorjanijournal/article-1-572-en.html
URL: http://goums.ac.ir/jorjanijournal/article-1-572-en.html
1- Department of Genetics, Faculty of Basic Sciences, Shahrekord Islamic Azad University, Shahrekord, Iran.
2- Department of Genetics, Faculty of Basic Sciences, Shahrekord Islamic Azad University, Shahrekord, Iran. , parisa_mohamadynejad@yahoo.com
3- Department of Genetics, Faculty of Basic Sciences, Kazerun Islamic Azad University, kazerun, Iran.
2- Department of Genetics, Faculty of Basic Sciences, Shahrekord Islamic Azad University, Shahrekord, Iran. , parisa_mohamadynejad@yahoo.com
3- Department of Genetics, Faculty of Basic Sciences, Kazerun Islamic Azad University, kazerun, Iran.
Abstract: (9008 Views)
Background and objectives: One of the latest studies in the genetics field is the evaluation of role of micro-RNAs as a biomarker for diagnosis of multiple sclerosis (MS), which is a demyelinating disease of the central nervous system (CNS) and emerges in the form of numerous small and large plaques in white matter in the brain and spinal cord. This disease could be associated with several complications, including reduced vision, spasticity and imbalance, and impaired sphincter control. MiR-202-3p is an intronic miRNA located in the ADA (Adenosine Deaminase) gene, which is the main enzyme involved in the pathway for the conversion of adenosine into inosine. Moreover, ADA regulates the inflammatory response and protection of tissue from damage as a strong complementary mechanism. This study aimed to evaluate the expression level of miR-202-3p in individuals diagnosed with relapsing-remitting multiple sclerosis (RRMS) and healthy individuals in Isfahan, Iran.
Methods: This analytical-observatory study was performed on 49 RRMS patients and 52 healthy individuals with no history of autoimmune and inflammatory diseases. Total RNA was extracted from blood lymphocytes by Ficoll and Trizol. Afterwards, cDNA was formed using a special miRNA cDNA kit, followed by the application of Real-time RT PCR to measure the expression of miR-202-3p in healthy individuals and patients.
Results: According to the results, the miR-202-3p expression was higher in patients, compared to healthy individuals (P=0.006). In addition, the sensitivity and diagnostic value of this miRNA in receiver operating characteristic (ROC) curve analysis were equal to AUC=0.80 (area under the curve).
Conclusion: In line with other studies, our findings demonstrated that miR-2023p can be used as a biomarker in the diagnosis of MS. In addition, it seems that miR-202-3p acts as an immunosuppressant by inhibiting ADA gene, which regulates various processes related to inflammatory response and maintenance of tissue from damage.
Methods: This analytical-observatory study was performed on 49 RRMS patients and 52 healthy individuals with no history of autoimmune and inflammatory diseases. Total RNA was extracted from blood lymphocytes by Ficoll and Trizol. Afterwards, cDNA was formed using a special miRNA cDNA kit, followed by the application of Real-time RT PCR to measure the expression of miR-202-3p in healthy individuals and patients.
Results: According to the results, the miR-202-3p expression was higher in patients, compared to healthy individuals (P=0.006). In addition, the sensitivity and diagnostic value of this miRNA in receiver operating characteristic (ROC) curve analysis were equal to AUC=0.80 (area under the curve).
Conclusion: In line with other studies, our findings demonstrated that miR-2023p can be used as a biomarker in the diagnosis of MS. In addition, it seems that miR-202-3p acts as an immunosuppressant by inhibiting ADA gene, which regulates various processes related to inflammatory response and maintenance of tissue from damage.
Type of Article: Original article |
Subject:
General medicine
Received: 2018/04/6 | Accepted: 2018/07/23 | Published: 2018/12/9
Received: 2018/04/6 | Accepted: 2018/07/23 | Published: 2018/12/9
References
1. Rowland LP. Molecular genetics, pseudogenetics, and clinical neurology: The Robert Wartenberg Lecture. Neurology. 1983;33(9):1179-. [DOI:10.1212/WNL.33.9.1179]
2. Olek M. Multiple sclerosis: etiology, diagnosis, and new treatment strategies: Springer; 2007.
3. Buc M. Role of regulatory T cells in pathogenesis and biological therapy of multiple sclerosis. Mediators of inflammation. 2013;2013. [DOI:10.1155/2013/963748]
4. Dutta R, Trapp BD. Pathogenesis of axonal and neuronal damage in multiple sclerosis. Neurology. 2007;68(22 suppl 3):S22-S31. [DOI:10.1212/01.wnl.0000275229.13012.32]
5. Minagar A, Alexander JS. Blood-brain barrier disruption in multiple sclerosis. Multiple Sclerosis Journal. 2003;9(6):540-9. [DOI:10.1191/1352458503ms965oa]
6. Alcalde-Cabero E, Almazán-Isla J, GarcíaMerino A, de Sá J, de Pedro-Cuesta J. Incidence of multiple sclerosis among European Economic Area populations, 1985-2009: the framework for monitoring. BMC neurology. 2013;13(1):58. [DOI:10.1186/1471-2377-13-58]
7. Izadi S, Nikseresht A, Sharifian M, Sahraian MA, Jahromi AH, Aghighi M, et al. Significant increase in the prevalence of multiple sclerosis in iran in 2011. Iranian journal of medical sciences. 2014;39(2):152.
8. Ramagopalan SV, Dyment DA, Valdar W, Herrera BM, Criscuoli M, Yee IML, et al. Autoimmune disease in families with multiple sclerosis: a population-based study. The Lancet Neurology. 2007;6(7):604-10. [DOI:10.1016/S1474-4422(07)70132-1]
9. Van Horssen J, Witte ME, Schreibelt G, De Vries HE. Radical changes in multiple sclerosis pathogenesis. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 2011;1812(2):141-50. [DOI:10.1016/j.bbadis.2010.06.011]
10. Farhana L, Dawson MI, Murshed F, Das JK, Rishi AK, Fontana JA. Upregulation of miR-150* and miR-630 induces apoptosis in pancreatic cancer cells by targeting IGF-1R. PloS one. 2013;8(5):e61015. [DOI:10.1371/journal.pone.0061015]
11. Huang Z, Huang S, Wang Q, Liang L, Ni S, Wang L, et al. MicroRNA-95 promotes cell proliferation and targets sorting Nexin 1 in human colorectal carcinoma. Cancer research. 2011. [DOI:10.1158/0008-5472.CAN-10-3032]
12. Schreiber-Agus N, Chin L, Chen K, Torres R, Rao G, Guida P, et al. An amino-terminal domain of Mxi1 mediates anti-Myc oncogenic activity and interacts with a homolog of the yeast transcriptional repressor SIN3. Cell. 1995;80(5):777-86. [DOI:10.1016/0092-8674(95)90356-9]
13. Gehring S, Rottmann S, Menkel AR, Mertsching J, Krippner-Heidenreich A, Lüscher B. Inhibition of proliferation and apoptosis by the transcriptional repressor Mad1 Repression of Fasinduced caspase-8 activation. Journal of Biological chemistry. 2000;275(14):10413-20. [DOI:10.1074/jbc.275.14.10413]
14. Hurlin P, Foley K, Ayer D, Eisenman R, Hanahan D, Arbeit J. Regulation of Myc and Mad during epidermal differentiation and HPVassociated tumorigenesis. Oncogene. 1995;11(12):2487-501.
15. Grandori C, Cowley SM, James LP, Eisenman RN. The Myc/Max/Mad network and the transcriptional control of cell behavior. Annual review of cell and developmental biology. 2000;16(1):653-99. [DOI:10.1146/annurev.cellbio.16.1.653]
16. Lüscher B. MAD1 and its life as a MYC antagonist: an update. European journal of cell biology. 2012;91(6-7):506-14. [DOI:10.1016/j.ejcb.2011.07.005]
17. Jiang Z, Guo J, Xiao B, Miao Y, Huang R, Li D, et al. Increased expression of miR-421 in human gastric carcinoma and its clinical association. Journal of gastroenterology. 2010;45(1):17-23. [DOI:10.1007/s00535-009-0135-6]
18. Zhao Y, Li C, Wang M, Su L, Qu Y, Li J, et al. Decrease of miR-202-3p expression, a novel tumor suppressor, in gastric cancer. Plos one. 2013;8(7):e69756. [DOI:10.1371/journal.pone.0069756]
19. Yu J, Qiu X, Shen X, Shi W, Wu X, Gu G, et al. miR-202 expression concentration and its clinical significance in the serum of multiple myeloma patients. Annals of clinical biochemistry. 2014;51(5):543-9. [DOI:10.1177/0004563213501155]
20. Ratech H, Thorbecke GJ, Meredith G, Hirschhorn R. Comparison and possible homology of isozymes of adenosine deaminase in Aves and humans. Enzyme. 1981;26:74-84. [DOI:10.1159/000459153]
21. Ungerer J, Oosthuizen H, Bissbort S, Vermaak W. Serum adenosine deaminase: isoenzymes and diagnostic application. Clinical Chemistry. 1992;38(7):1322-6.
22. Maier SA, Galellis JR, McDermid HE. Phylogenetic analysis reveals a novel protein family closely related to adenosine deaminase. Journal of molecular evolution. 2005;61(6):776- 94. [DOI:10.1007/s00239-005-0046-y]
23. Zavialov AV, Engström Å. Human ADA2 belongs to a new family of growth factors with adenosine deaminase activity. Biochemical Journal. 2005;391(1):51-7. [DOI:10.1042/BJ20050683]
24. Tritsch GL, Niswander PW. Adenosine deaminase activity and superoxide formation during phagocytosis and membrane perturbation of macrophages. Immunological communications. 1981;10(1):1-7. [DOI:10.3109/08820138109050681]
25. Sitkovsky MV, Ohta A. The 'danger'sensors that STOP the immune response: the A2 adenosine receptors? Trends in immunology. 2005;26(6):299-304. [DOI:10.1016/j.it.2005.04.004]
26. Haskó G, Cronstein BN. Adenosine: an endogenous regulator of innate immunity. Trends in immunology. 2004;25(1):33-9. [DOI:10.1016/j.it.2003.11.003]
27. Fredholm B. Adenosine, an endogenous distress signal, modulates tissue damage and repair. Cell death and differentiation. 2007;14(7):1315. [DOI:10.1038/sj.cdd.4402132]
28. Antonioli L, Fornai M, Colucci R, Ghisu N, Tuccori M, Del Tacca M, et al. Regulation of enteric functions by adenosine: pathophysiological and pharmacological implications. Pharmacology & therapeutics. 2008;120(3):233-53. [DOI:10.1016/j.pharmthera.2008.08.010]
29. Daddona PE. Human adenosine deaminase. Properties and turnover in cultured T and B lymphoblasts. Journal of Biological Chemistry. 1981;256(23):12496-501.
30. Aldrich MB, Blackburn MR, Kellems RE. The importance of adenosine deaminase for lymphocyte development and function. Biochemical and biophysical research communications. 2000;272(2):311-5. [DOI:10.1006/bbrc.2000.2773]
31. Franco R, Pacheco R, Gatell JM, Gallart T, Lluis C. Enzymatic and extraenzymatic role of adenosine deaminase 1 in T-cell-dendritic cell contacts and in alterations of the immune function. Critical Reviews™ in Immunology. 2007;27(6). [DOI:10.1615/CritRevImmunol.v27.i6.10]
32. Hasko G, Szabó C, Németh ZH, Kvetan V, Pastores S, Vizi ES. Adenosine receptor agonists differentially regulate IL-10, TNF-alpha, and nitric oxide production in RAW 264.7 macrophages and in endotoxemic mice. The Journal of Immunology. 1996;157(10):4634-40.
33. Németh ZH, Lutz CS, Csóka B, Deitch EA, Leibovich SJ, Gause WC, et al. Adenosine augments IL-10 production by macrophages through an A2B receptor-mediated posttranscriptional mechanism. The Journal of Immunology. 2005;175(12):8260-70. [DOI:10.4049/jimmunol.175.12.8260]
34. Csóka B, Németh ZH, Virág L, Gergely P, Leibovich SJ, Pacher P, et al. A2A adenosine receptors and C/EBPβ are crucially required for IL-10 production by macrophages exposed to Escherichia coli. Blood. 2007;110(7):2685-95. [DOI:10.1182/blood-2007-01-065870]
35. Blackburn MR, Kellems RE. Adenosine deaminase deficiency: metabolic basis of immune deficiency and pulmonary inflammation. Advances in immunology. 86: Elsevier; 2005. p. 1-41. [DOI:10.1016/S0065-2776(04)86001-2]
36. Nathan C. Points of control in inflammation. Nature. 2002;420(6917):846. [DOI:10.1038/nature01320]
37. Schratt GM, Tuebing F, Nigh EA, Kane CG, Sabatini ME, Kiebler M, et al. A brain-specific microRNA regulates dendritic spine development. nature. 2006;439(7074):283. [DOI:10.1038/nature04367]
38. Cohen JE, Lee PR, Chen S, Li W, Fields RD. MicroRNA regulation of homeostatic synaptic plasticity. Proceedings of the National Academy of Sciences. 2011;108(28):11650-5. [DOI:10.1073/pnas.1017576108]
39. Dugas JC, Notterpek L. MicroRNAs in oligodendrocyte and Schwann cell differentiation. Developmental neuroscience. 2011;33(1):14-20. [DOI:10.1159/000323919]
40. Barca-Mayo O, Lu QR. Fine-tuning oligodendrocyte development by microRNAs. Frontiers in neuroscience. 2012;6. [DOI:10.3389/fnins.2012.00013]
41. He X, Yu Y, Awatramani R, Lu QR. Unwrapping myelination by microRNAs. The Neuroscientist. 2012;18(1):45-55. [DOI:10.1177/1073858410392382]
42. Zhao X, He X, Han X, Yu Y, Ye F, Chen Y, et al. MicroRNA-mediated control of oligodendrocyte differentiation. Neuron. 2010;65(5):612-26. [DOI:10.1016/j.neuron.2010.02.018]
43. Svaren J. MicroRNA and transcriptional crosstalk in myelinating glia. Neurochemistry international. 2014;77:50-7. [DOI:10.1016/j.neuint.2014.06.010]
44. Lasley RD, Mentzer RM. Myocardial protection: the adenosine story. Drug development research. 1996;39(3‐4):314-8.
https://doi.org/10.1002/(SICI)1098-2299(199611/12)39:3/4<314::AID-DDR11>3.0.CO;2-1 [DOI:10.1002/(SICI)1098-2299(199611/12)39:3/43.0.CO;2-1]
45. Cristalli G, Costanzi S, Lambertucci C, Lupidi G, Vittori S, Volpini R, et al. Adenosine deaminase: functional implications and different classes of inhibitors. Medicinal research reviews. 2001;21(2):105-28.
https://doi.org/10.1002/1098-1128(200103)21:2<105::AID-MED1002>3.0.CO;2-U [DOI:10.1002/1098-1128(200103)21:23.0.CO;2-U]
46. Honma Y. A novel therapeutic strategy against monocytic leukemia with deoxyadenosine analogs and adenosine deaminase inhibitors. Leukemia & lymphoma. 2001;42(5):953-62. [DOI:10.3109/10428190109097714]
47. Muddashetty R, Bassell GJ. A boost in microRNAs shapes up the neuron. The EMBO journal. 2009;28(6):617-8. [DOI:10.1038/emboj.2009.51]
48. Li J-S, Yao Z-X. MicroRNAs: novel regulators of oligodendrocyte differentiation and potential therapeutic targets in demyelination related diseases. Molecular neurobiology. 2012;45(1):200-12. [DOI:10.1007/s12035-011-8231-z]
49. Fischer D, Van der Weyden MB, Snyderman R, Kelley WN. A role for adenosine deaminase in human monocyte maturation. The Journal of clinical investigation. 1976;58(2):399-407. [DOI:10.1172/JCI108484]
50. Yagawa K, Okamura J. Role of adenosine deaminase in activation of macrophages. Infect Immun. 1981;32(1):394-7.
51. Tritsch GL, Niswander PW. Purine catabolism as a source of superoxide in macrophages. Ann N Y Acad Sci. 1985;451:279-90. [DOI:10.1111/j.1749-6632.1985.tb27119.x]
52. Sun Z, Zhang T, Hong H, Liu Q, Zhang H. miR-202 suppresses proliferation and induces apoptosis of osteosarcoma cells by downregulating Gli2. Mol Cell Biochem. 2014;397(1-2):277-83. [DOI:10.1007/s11010-014-2195-z]
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