MicroRNA-125b: association with disease activity and the treatment response of patients with early rheumatoid arthritis
Language English Country England, Great Britain Media electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
27255643
PubMed Central
PMC4890522
DOI
10.1186/s13075-016-1023-0
PII: 10.1186/s13075-016-1023-0
Knihovny.cz E-resources
- Keywords
- Disease activity, Early rheumatoid arthritis, MicroRNA-125b, Treatment outcome,
- MeSH
- Antirheumatic Agents therapeutic use MeSH
- Biomarkers analysis MeSH
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- MicroRNAs analysis MeSH
- Area Under Curve MeSH
- Arthritis, Rheumatoid blood drug therapy genetics MeSH
- ROC Curve MeSH
- Aged MeSH
- Treatment Outcome MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antirheumatic Agents MeSH
- Biomarkers MeSH
- MicroRNAs MeSH
- MIRN125 microRNA, human MeSH Browser
BACKGROUND: MicroRNAs (miRNAs) are small RNAs that regulate gene expression by targeting mRNA. It was proved that some miRNAs are significantly deregulated in rheumatoid arthritis (RA). MicroRNA-125b negatively regulates expression of TNF-α, which plays a crucial role in RA pathogenesis. The aim of this study was to determine the treatment outcome of patients with early RA based on the expression of circulating and cellular miR-125b. METHODS: Total RNA was isolated from the plasma and peripheral blood mononuclear cells (PBMCs) of 58 patients with early RA before and three months after treatment initiation and of 54 age- and sex-matched healthy controls (HC). The expression of miR-125b was measured by TaqMan quantitative PCR. The treatment responders were defined as patients achieving remission or low disease activity (28-joint count disease activity score (DAS28) <3.2). Receiver operating characteristic (ROC) curve and stepwise backward multivariable logistic regression analyses of miR-125b expression were used to predict the disease outcome at three and six months after initiation of treatment. RESULTS: The expression of miR-125b in the PBMCs and plasma of treatment-naïve early RA patients was significantly lower than that of HC and increased significantly after three months of treatment, particularly in responders. However, only the cellular expression of miR-125b was inversely correlated with disease activity. MiR-125b expression in PBMCs was higher in responders than in non-responders after three months (p = 0.042). Using ROC analysis, the cellular expression of miR-125b, but not the disease activity at baseline, predicted the treatment response after three months of therapy (area under the curve 0.652 (95 % CI 0.510 to 0.793); p = 0.048). CONCLUSION: The expression of miR-125b in PBMCs of treatment-naïve patients may present a novel biomarker for monitoring the treatment outcome during the early phase of RA.
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McInnes IB, O'Dell JR. State-of-the-art: rheumatoid arthritis. Ann Rheum Dis. 2010;69:1898–906. doi: 10.1136/ard.2010.134684. PubMed DOI
Stoffer MA, Schoels MM, Smolen JS, Aletaha D, Breedveld FC, Burmester G, et al. Evidence for treating rheumatoid arthritis to target: results of a systematic literature search update. Ann Rheum Dis. 2016;75:16–22. doi: 10.1136/annrheumdis-2015-207526. PubMed DOI PMC
van Eijk IC, Nielen MM, van der Horst-Bruinsma I, Tijhuis GJ, Boers M, Dijkmans BA, et al. Aggressive therapy in patients with early arthritis results in similar outcome compared with conventional care: the STREAM randomized trial. Rheumatology (Oxford) 2012;51:686–94. doi: 10.1093/rheumatology/ker355. PubMed DOI PMC
Hobbs KF, Cohen MD. Rheumatoid arthritis disease measurement: a new old idea. Rheumatology (Oxford) 2012;51(Suppl 6):vi21–7. doi: 10.1093/rheumatology/kes282. PubMed DOI
Migliore C, Giordano S. Resistance to targeted therapies: a role for microRNAs? Trends Mol Med. 2013;19:633–42. doi: 10.1016/j.molmed.2013.08.002. PubMed DOI
Jüngel A, Ospelt C, Gay S. What can we learn from epigenetics in the year 2009? Curr Opin Rheumatol. 2010;22:284–92. doi: 10.1097/BOR.0b013e3283389641. PubMed DOI
Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136:215–33. doi: 10.1016/j.cell.2009.01.002. PubMed DOI PMC
O'Connell RM, Rao DS, Baltimore D. microRNA regulation of inflammatory responses. Annu Rev Immunol. 2012;30:295–312. doi: 10.1146/annurev-immunol-020711-075013. PubMed DOI
Lujambio A, Lowe SW. The microcosmos if cancer. Nature. 2012;482:347–55. doi: 10.1038/nature10888. PubMed DOI PMC
Romaine SPR, Tomaszewski M, Condorelli G, Samani NJ. MicroRNAs in cardiovascular disease: an introduction for clinicians. Heart. 2015;101:921–8. doi: 10.1136/heartjnl-2013-305402. PubMed DOI PMC
Duroux-Richard I, Jorgensen C, Apparailly F. What do microRNAs mean for rheumatoid arthritis? Arthritis Rheum. 2012;64:11–20. doi: 10.1002/art.30651. PubMed DOI
Baxter D, McInnes IB, Kurowska-Stolarska M. Novel regulatory mechanisms in inflammatory arthritis: a role for microRNA. Immunol Cell Biol. 2012;90:288–92. doi: 10.1038/icb.2011.114. PubMed DOI
Filková M, Jüngel A, Gay RE, Gay S. MicroRNAs in rheumatoid arthritis: potential role in diagnosis and therapy. BioDrugs. 2012;26:131–41. doi: 10.2165/11631480-000000000-00000. PubMed DOI
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 USA. 2008;105:10513–8. doi: 10.1073/pnas.0804549105. PubMed DOI PMC
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:R86. doi: 10.1186/ar3013. PubMed DOI PMC
Filková M, Aradi B, Senolt 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;73:1898–904. doi: 10.1136/annrheumdis-2012-202815. PubMed DOI PMC
Wang H, Tan G, Dong L, Cheng L, Li K, Wang Z, et al. Circulating MiR-125b as a marker predicting chemoresistance in breast cancer. PLoS One. 2012;7:e34210. doi: 10.1371/journal.pone.0034210. PubMed DOI PMC
Duroux-Richard I, Pers YM, Fabre S, Ammari M, Baeten D, Cartron G, et al. Circulating miR-125b is a potential biomarker predicting response to rituximab in rheumatoid arthritis. Mediators Inflamm. 2014;2014:342524. doi: 10.1155/2014/342524. PubMed DOI PMC
Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, 3rd, et al. 2010 rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis. 2010;69:1580–8. doi: 10.1136/ard.2010.138461. PubMed DOI
Sglunda O, Mann H, Hulejová H, Kuklová M, Pecha O, Pleštilová L, et al. Decreased circulating visfatin is associated with improved disease activity in early rheumatoid arthritis: data from the PERAC cohort. PLoS One. 2014;9:e103495. doi: 10.1371/journal.pone.0103495. PubMed DOI PMC
Churov AV, Oleinik EK, Knip M. MicroRNAs in rheumatoid arthritis: Altered expression and diagnostic potential. Autoimmun Rev. 2015;14:1029–37. doi: 10.1016/j.autrev.2015.07.005. PubMed DOI
Xu N, Brodin P, Wei T, Meisgen F, Eidsmo L, Nagy N, et al. MiR-125b, a MicroRNA downregulated in psoriasis, modulates keratinocyte proliferation by targeting FGFR2. J Invest Dermatol. 2011;131:1521–9. doi: 10.1038/jid.2011.55. PubMed DOI
Luo X, Zhang L, Li M, Zhang W, Leng X, Zhang F, et al. The role of miR-125b in T lymphocytes in the pathogenesis of systemic lupus erythematosus. Clin Exp Rheumatol. 2013;31:263–71. PubMed
Tili E, Michaille J, Cimino A, Costinean S, Dumitru CD, Adair B, et al. Modulation of miR-155 and miR-125b levels following lipopolysacharide/TNFα stimulation and their possible roles in regulating the response to endotoxin shock. J Immunol. 2007;179:5082–9. doi: 10.4049/jimmunol.179.8.5082. PubMed DOI
Rajaram MV, Ni B, Morris JD, Brooks MN, Carlson TK, Bakthavachalu B, et al. Mycobacterium tuberculosis lipomannan blocks TNF biosynthesis by regulating macrophage MAPK-activated protein kinase 2 (MK2) and microRNA miR-125b. Proc Natl Acad Sci USA. 2011;108:17408–13. doi: 10.1073/pnas.1112660108. PubMed DOI PMC
Huang HC, Yu HR, Huang LT, Huang HC, Chen RF, Lin IC, et al. miR-125b regulates TNF- production in CD14+ neonatal monocytes via post-transcriptional regulation. J Leukoc Biol. 2012;92:171–82. doi: 10.1189/jlb.1211593. PubMed DOI
Rossi RL, Rossetti G, Wenandy L, Curti S, Ripamonti A, Bonnal RJ, et al. Distinct microRNA signatures in human lymphocyte subsets and enforcement of the naive state in CD4+ T cells by the microRNA miR-125b. Nat Immunol. 2011;12:796–803. doi: 10.1038/ni.2057. PubMed DOI
Atarod S, Smith H, Dickinson A, Wang XN. Important considerations for microRNA extraction methods from whole blood and peripheral blood mononuclear cells. F1000Res. 2014;3:183. PubMed PMC
Cheng NL, Chen X, Kim J, Shi AH, Nguyen C, Wersto R, et al. MicroRNA-125b modulates inflammatory chemokine CCL4 expression in immune cells and its reduction causes CCL4 increase with age. Aging Cell. 2015;14:200–8. doi: 10.1111/acel.12294. PubMed DOI PMC
Castro-Villegas C, Pérez-Sánchez C, Escudero A, Filipescu I, Verdu M, Ruiz-Limón P, et al. Circulating miRNAs as potential biomarkers of therapy effectiveness in rheumatoid arthritis patients treated with anti-TNFα. Arthritis Res Ther. 2015;17:49. doi: 10.1186/s13075-015-0555-z. PubMed DOI PMC
Murray MY, Rushworth SA, Zaitseva L, Bowles KM, MacEwan DJ. Attenuation of dexamethasone-induced cell death in multiple myeloma is mediated by miR-125b expression. Cell Cycle. 2013;12:2144–53. doi: 10.4161/cc.25251. PubMed DOI PMC
Yin H, Sun Y, Wang X, Park J, Zhang Y, Li M, et al. Progress on the relationship between miR-125 family and tumorigenesis. Exp Cell Res. 2015;339:252–60. doi: 10.1016/j.yexcr.2015.09.015. PubMed DOI
Is there a potential of circulating miRNAs as biomarkers in rheumatic diseases?