Plasma Levels of MicroRNA-146a-5p, MicroRNA-24-3p, and MicroRNA-125a-5p as Potential Diagnostic Biomarkers for Rheumatoid Arthris
Diagnostic Biomarkers for Rheumatoid Arthritis
-
Fatemeh Safari
,
Elia Damavandi
,
Abdol-Rahman Rostamian
,
Shafieh Movassaghi
,
Zeinab Imani-Saber
,
Mojtaba Saffari
,
Majid Kabuli
,
Mohsen Ghadami
Abstract
Rheumatoid arthritis (RA) is an autoimmune disease that is characterized by inflammation of the articular tissue. This study aims to evaluate the expression of microRNA (miR)-146a-5p, miR-24-3p, and miR-125a-5p in the plasma of RA patients and compare them with those of healthy controls to obtain a specific expression profile for earlier diagnosis and assistance in treating patients.
This study was performed on 50 RA patients and 50 healthy controls. Five microliters of blood were taken from each patient/control. Plasma RNA was extracted using the Trisol solution. cDNAs were synthesized; using moloney murine leukemia virus (MMLV) and deoxynucleoside triphosphate (dNTP). Real-time PCR was performed using SYBR green kit.
The mean expression of miR-146a-5p, miR-24-3p, and miR-125a-5p in the RA group were 8.1±1.9, 6.5±1.2, and 6.8±2.2 and in the healthy group were 4.8±1.6, 3.6±2.2, and 3.4±1.7, respectively. Significant differences were also observed in the mean expression of these three miRNAs in four subgroups of RA patients with different disease activity based on disease activity score 28 (DAS28) (p<0.05). ROC curve analysis showed that miR-146a-5p (AUC=0.8, sensitivity= 96%, specificity=86%), miR-24-3p (AUC=0.7, Sensitivity=95%, Specificity=75%) and miR-125a-5p (AUC=0.71, sensitivity=93%, specificity=84%) could be used as suitable biomarkers for RA diagnosis.
Increased expressions of miR-146a-5p, miR-24-3p, and miR-125a-5p in RA patients indicate that the miRNAs are involved in disease incidence and progression, and the measurement of their expression can play an essential role in the diagnosis and treatment of the disease.
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8. Long H, Wang X, Chen Y, Wang L, Zhao M, Lu Q. Dysregulation of microRNAs in autoimmune diseases: Pathogenesis, biomarkers and potential therapeutic targets. Cancer Lett. 2018;428:90-103.
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19. Nakasa T, Miyaki S, Okubo A, Hashimoto M, Nishida K, Ochi M, et al. Expression of microRNA‐146 in rheumatoid arthritis synovial tissue. Arthritis Rheumatol. 2008;58(5):1284-92.
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21. Nakamachi Y, Kawano S, Takenokuchi M, Nishimura K, Sakai Y, Chin T, et al. MicroRNA‐124a is a key regulator of proliferation and monocyte chemoattractant protein 1 secretion in fibroblast‐like synoviocytes from patients with rheumatoid arthritis. Arthritis Rheumatol. 2009;60(5):1294-304.
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24. Niu X, He D, Zhang X, Yue T, Li N, Zhang JZ, et al. IL-21 regulates Th17 cells in rheumatoid arthritis. Hum Immunol. 2010;71(4):334-41.
25. O'Dell JR. Treating rheumatoid arthritis early: a window of opportunity? Arthritis Rheumatol. 2002;46(2):283-5.
26. Visser H, Le Cessie S, Vos K, Breedveld FC, Hazes JM. How to diagnose rheumatoid arthritis early: a prediction model for persistent (erosive) arthritis. Arthritis Rheumatol. 2002;46(2):357-65.
27. Etheridge A, Lee I, Hood L, Galas D, Wang K. Extracellular microRNA: a new source of biomarkers. Mutat Res. 2011;717(1-2):85-90.
28. Mookherjee N, El-Gabalawy HS. High degree of correlation between whole blood and PBMC expression levels of miR-155 and miR-146a in healthy controls and rheumatoid arthritis patients. J Immunol Methods. 2013;400:106-10.
29. Furer V, Greenberg JD, Attur M, Abramson SB, Pillinger MH. The role of microRNA in rheumatoid arthritis and other autoimmune diseases. Clin Immunol. 2010;136(1):1-15.
30. Rusca N, Monticelli S. MiR-146a in immunity and disease. J Mol Biol. 2011;2011.
31. Kriegsmann M, Randau TM, Gravius S, Lisenko K, Altmann C, Arens N, et al. Expression of miR-146a, miR-155, and miR-223 in formalin-fixed paraffin-embedded synovial tissues of patients with rheumatoid arthritis and osteoarthritis. Virchows Arch. 2016;469(1):93-100.
32. Abou-Zeid A, Saad M, Soliman E. MicroRNA 146a expression in rheumatoid arthritis: association with tumor necrosis factor–alpha and disease activity. Genet Test Mol Biomarkers. 2011;15(11):807-12.
33. Ormseth MJ, Solus JF, Vickers KC, Oeser AM, Raggi P, Stein CM. Utility of select plasma microRNA for disease and cardiovascular risk assessment in patients with rheumatoid arthritis. J Rheumatol. 2015;42(10):1746-51.
34. Elsayed HMA, Khater WS, Ibrahim AA, Hamdy MSE-d, Morshedy NA. MicroRNA-146a expression as a potential biomarker for rheumatoid arthritis in Egypt. Egypt J Med Hum Genet. 2017;18(2):173-9.
35. Fleischmann RM, van der Heijde D, Gardiner PV, Szumski A, Marshall L, Bananis E. DAS28-CRP and DAS28-ESR cut-offs for high disease activity in rheumatoid arthritis are not interchangeable. RMD Open. 2017;3(1).
2. NG KP, AUSTIN P, AMERATUNGA R, McQUEEN F. Role of anticyclic citrullinated peptide 2 assay in long‐standing rheumatoid arthritis. APLAR Journal of Rheumatology. 2006;9(3):211-5.
3. Dashti N, Javadi Z, Safari F, Farahvash S, Zarebavani M. Estimation of Diagnostic Markers in Rheumatoid Arthritis and Ankylosing Spondylitis. Clin Lab. 2017;63(4):797-800.
4. Edwards C, Cooper C. Early environmental factors and rheumatoid arthritis. Clin Exp Immunol. 2006;143(1):1-5.
5. Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham III CO, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Arthritis Rheumatol. 2010;62(9):2569-81.
6. Arnett FC, Edworthy SM, Bloch DA, Mcshane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31(3):315-24.
7. Mjaavatten MD, Bykerk VP. Early rheumatoid arthritis: the performance of the 2010 ACR/EULAR criteria for diagnosing RA. Best Pract Res Clin Rheumato. 2013;27(4):451-66.
8. Long H, Wang X, Chen Y, Wang L, Zhao M, Lu Q. Dysregulation of microRNAs in autoimmune diseases: Pathogenesis, biomarkers and potential therapeutic targets. Cancer Lett. 2018;428:90-103.
9. Pauley KM, Cha S, Chan EK. MicroRNA in autoimmunity and autoimmune diseases. J Autoimmun. 2009;32(3-4):189-94.
10. Paradowska-Gorycka A, Stypińska B. The role of cell-free circulating microRNA in diagnostics in patients with rheumatoid arthritis. Reumatol. 2016;54(3):95.
11. Sonkoly E, Ståhle M, Pivarcsi A, editors. MicroRNAs and immunity: novel players in the regulation of normal immune function and inflammation. Seminars in cancer biology; 2008: Elsevier.
12. Murata K, Furu M, Yoshitomi H, Ishikawa M, Shibuya H, Hashimoto M, et al. Comprehensive microRNA analysis identifies miR-24 and miR-125a-5p as plasma biomarkers for rheumatoid arthritis. PLOS ONE. 2013;8(7):e69118.
13. Mitchell PS, Parkin RK, Kroh EM, Fritz BR, Wyman SK, Pogosova-Agadjanyan EL, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci. 2008;105(30):10513-8.
14. Duroux‐Richard I, Jorgensen C, Apparailly F. What do microRNAs mean for rheumatoid arthritis? Arthritis Rheumatol. 2012;64(1):11-20.
15. Pauley KM, Satoh M, Chan AL, Bubb MR, Reeves WH, Chan EK. Upregulated miR-146a expression in peripheral blood mononuclear cells from rheumatoid arthritis patients. Arthritis Res Ther. 2008;10(4):1-10.
16. Murata K, Yoshitomi H, Tanida S, Ishikawa M, Nishitani K, Ito H, et al. Plasma and synovial fluid microRNAs as potential biomarkers of rheumatoid arthritis and osteoarthritis. Arthritis Res Ther. 2010;12(3):1-14.
17. Li J, Wan Y, Guo Q, Zou L, Zhang J, Fang Y, et al. Altered microRNA expression profile with miR-146a upregulation in CD4+ T cells from patients with rheumatoid arthritis. Arthritis Res Ther. 2010;12(3):1-12.
18. Niimoto T, Nakasa T, Ishikawa M, Okuhara A, Izumi B, Deie M, et al. MicroRNA-146a expresses in interleukin-17 producing T cells in rheumatoid arthritis patients. BMC Musculoskelet Disord. 2010;11(1):1-11.
19. Nakasa T, Miyaki S, Okubo A, Hashimoto M, Nishida K, Ochi M, et al. Expression of microRNA‐146 in rheumatoid arthritis synovial tissue. Arthritis Rheumatol. 2008;58(5):1284-92.
20. Stanczyk J, Pedrioli DML, Brentano F, Sanchez‐Pernaute O, Kolling C, Gay RE, et al. Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis. Arthritis Rheumatol. 2008;58(4):1001-9.
21. Nakamachi Y, Kawano S, Takenokuchi M, Nishimura K, Sakai Y, Chin T, et al. MicroRNA‐124a is a key regulator of proliferation and monocyte chemoattractant protein 1 secretion in fibroblast‐like synoviocytes from patients with rheumatoid arthritis. Arthritis Rheumatol. 2009;60(5):1294-304.
22. Sharbati-Tehrani S, Kutz-Lohroff B, Bergbauer R, Scholven J, Einspanier R. miR-Q: a novel quantitative RT-PCR approach for the expression profiling of small RNA molecules such as miRNAs in a complex sample. BMC Mol Biol. 2008;9(1):1-13.
23. Filková M, Aradi B, Šenolt L, Ospelt C, Vettori S, Mann H, et al. Association of circulating miR-223 and miR-16 with disease activity in patients with early rheumatoid arthritis. Ann Rheum Dis. 2014;73(10):1898-904.
24. Niu X, He D, Zhang X, Yue T, Li N, Zhang JZ, et al. IL-21 regulates Th17 cells in rheumatoid arthritis. Hum Immunol. 2010;71(4):334-41.
25. O'Dell JR. Treating rheumatoid arthritis early: a window of opportunity? Arthritis Rheumatol. 2002;46(2):283-5.
26. Visser H, Le Cessie S, Vos K, Breedveld FC, Hazes JM. How to diagnose rheumatoid arthritis early: a prediction model for persistent (erosive) arthritis. Arthritis Rheumatol. 2002;46(2):357-65.
27. Etheridge A, Lee I, Hood L, Galas D, Wang K. Extracellular microRNA: a new source of biomarkers. Mutat Res. 2011;717(1-2):85-90.
28. Mookherjee N, El-Gabalawy HS. High degree of correlation between whole blood and PBMC expression levels of miR-155 and miR-146a in healthy controls and rheumatoid arthritis patients. J Immunol Methods. 2013;400:106-10.
29. Furer V, Greenberg JD, Attur M, Abramson SB, Pillinger MH. The role of microRNA in rheumatoid arthritis and other autoimmune diseases. Clin Immunol. 2010;136(1):1-15.
30. Rusca N, Monticelli S. MiR-146a in immunity and disease. J Mol Biol. 2011;2011.
31. Kriegsmann M, Randau TM, Gravius S, Lisenko K, Altmann C, Arens N, et al. Expression of miR-146a, miR-155, and miR-223 in formalin-fixed paraffin-embedded synovial tissues of patients with rheumatoid arthritis and osteoarthritis. Virchows Arch. 2016;469(1):93-100.
32. Abou-Zeid A, Saad M, Soliman E. MicroRNA 146a expression in rheumatoid arthritis: association with tumor necrosis factor–alpha and disease activity. Genet Test Mol Biomarkers. 2011;15(11):807-12.
33. Ormseth MJ, Solus JF, Vickers KC, Oeser AM, Raggi P, Stein CM. Utility of select plasma microRNA for disease and cardiovascular risk assessment in patients with rheumatoid arthritis. J Rheumatol. 2015;42(10):1746-51.
34. Elsayed HMA, Khater WS, Ibrahim AA, Hamdy MSE-d, Morshedy NA. MicroRNA-146a expression as a potential biomarker for rheumatoid arthritis in Egypt. Egypt J Med Hum Genet. 2017;18(2):173-9.
35. Fleischmann RM, van der Heijde D, Gardiner PV, Szumski A, Marshall L, Bananis E. DAS28-CRP and DAS28-ESR cut-offs for high disease activity in rheumatoid arthritis are not interchangeable. RMD Open. 2017;3(1).
| Files | ||
| Issue | Vol 20 No 3 (2021) | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/ijaai.v20i3.6334 | |
| Keywords | ||
| MiR-146a MiR-24-3p Rheumatoid arthritis | ||
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How to Cite
1.
Safari F, Damavandi E, Rostamian A-R, Movassaghi S, Imani-Saber Z, Saffari M, Kabuli M, Ghadami M. Plasma Levels of MicroRNA-146a-5p, MicroRNA-24-3p, and MicroRNA-125a-5p as Potential Diagnostic Biomarkers for Rheumatoid Arthris. Iran J Allergy Asthma Immunol. 2021;20(3):326-337.
