A major challenge in multiple sclerosis (MS) is to develop biomarkers that could help in understanding individual MS patients, i.e. whether they are a responder or non-responder to therapy, which medicine is more effective, and the degree to which they may be entering the progressive phase of disease. In the last few years, a lot of attention has been drawn toward identification of diagnostic, prognostic, process-specific, and treatment-related biomarkers for MS. In this review, we will focus on the micro RNAs (miRNAs) as potential candidates for MS biomarkers.
OromUANielsenFCLundAH. MicroRNA-10a binds the 5′ UTR of ribosomal protein mRNAs and enhances their translation. Mol Cell2008; 30: 460–471.
2.
LytleJRYarioTASteitzJA. Target mRNAs are repressed as efficiently by microRNA-binding sites in the 5′ UTR as in the 3′ UTR. Proc Natl Acad Sci USA2007; 104: 9667–9672.
3.
ZhouXDuanXQianJ. Abundant conserved microRNA target sites in the 5′-untranslated region and coding sequence. Genetica2009; 137: 159–164.
4.
BartelDP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell2004; 116: 281–297.
5.
GhildiyalMXuJSeitzH. Sorting of Drosophila small silencing RNAs partitions microRNA* strands into the RNA interference pathway. RNA2010; 16: 43–56.
6.
OkamuraKPhillipsMDTylerDM. The regulatory activity of microRNA* species has substantial influence on microRNA and 3′ UTR evolution. Nat Struct Mol Biol2008; 15: 354–363.
EbertMSSharpPA. Roles for microRNAs in conferring robustness to biological processes. Cell2012; 149: 515–524.
9.
MendellJTOlsonEN. MicroRNAs in stress signaling and human disease. Cell2012; 148: 1172–1187.
10.
CortezMABueso-RamosCFerdinJ. MicroRNAs in body fluids – the mix of hormones and biomarkers. Nat Rev2011; 8: 467–477.
11.
ChimSSShingTKHungEC. Detection and characterization of placental microRNAs in maternal plasma. Clin Chem2008; 54: 482–490.
12.
KosakaNYoshiokaYHagiwaraK. Trash or treasure: extracellular microRNAs and cell-to-cell communication. Front Genet2013; 4: 173.
13.
ChenXBaYMaL. Characterization of microRNAs in serum: a novel class of biomarkers for diagnosis of cancer and other diseases. Cell Res2008; 18: 997–1006.
14.
MitchellPSParkinRKKrohEM. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci USA2008; 105: 10513–10518.
15.
Guerau-de-ArellanoMAlderHOzerHG. miRNA profiling for biomarker discovery in multiple sclerosis: from microarray to deep sequencing. J Neuroimmunol2012; 248: 32–39.
16.
MestdaghPHartmannNBaeriswylL. Evaluation of quantitative miRNA expression platforms in the microRNA quality control (miRQC) study. Nat Methods2014; 11: 809–815.
17.
JunkerAKrumbholzMEiseleS. MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47. Brain2009; 132: 3342–3352.
18.
StanczykJPedrioliDMBrentanoF. Altered expression of MicroRNA in synovial fibroblasts and synovial tissue in rheumatoid arthritis. Arthritis Rheum2008; 58: 1001–1009.
19.
DuCLiuCKangJ. MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat Immunol2009; 10: 1252–1259.
20.
OtaeguiDBaranziniSEArmananzasR. Differential micro RNA expression in PBMC from multiple sclerosis patients. PLoS One2009; 4: e6309.
21.
KellerALeidingerPLangeJ. Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsing–remitting disease from healthy controls. PLoS One2009; 4: e7440.
22.
SondergaardHBHesseDKrakauerM. Differential microRNA expression in blood in multiple sclerosis. Mult Scler2013; 19: 1849–1857.
23.
GandhiRHealyBGholipourT. Circulating microRNAs as biomarkers for disease staging in multiple sclerosis. Ann Neurol2013; 73: 729–740.
24.
KellerALeidingerPSteinmeyerF. Comprehensive analysis of microRNA profiles in multiple sclerosis including next-generation sequencing. Mult Scler2013: DOI: 10.1177/ 1352458513496343.
25.
Martinelli-BoneschiFFenoglioCBrambillaP. MicroRNA and mRNA expression profile screening in multiple sclerosis patients to unravel novel pathogenic steps and identify potential biomarkers. Neurosci Lett2012; 508: 4–8.
26.
CoxMBCairnsMJGandhiKS. MicroRNAs miR-17 and miR-20a inhibit T cell activation genes and are under-expressed in MS whole blood. PLoS One2010; 5: e12132.
OlssonTZhiWWHojebergB. Autoreactive T lymphocytes in multiple sclerosis determined by antigen-induced secretion of interferon-gamma. J Clin Invest1990; 86: 981–985.
29.
LockCHermansGPedottiR. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat Med2002; 8: 500–508.
30.
VoskuhlRRMartinRBergmanC. T helper 1 (Th1) functional phenotype of human myelin basic protein-specific T lymphocytes. Autoimmunity1993; 15: 137–143.
31.
De SantisGFerracinMBiondaniA. Altered miRNA expression in T regulatory cells in course of multiple sclerosis. J Neuroimmunol2010; 226: 165–171.
32.
LindbergRLHoffmannFMehlingM. Altered expression of miR-17–5p in CD4+ lymphocytes of relapsing-remitting multiple sclerosis patients. Eur J Immunol2010; 40: 888–898.
33.
XiaoCSrinivasanLCaladoDP. Lymphoproliferative disease and autoimmunity in mice with increased miR-17–92 expression in lymphocytes. Nat Immunol2008; 9: 405–414.
TsuchidaAOhnoSWuW. miR-92 is a key oncogenic component of the miR-17–92 cluster in colon cancer. Cancer Sci2011; 102: 2264–2271.
39.
GrigoryevYAKurianSMHartT. MicroRNA regulation of molecular networks mapped by global microRNA, mRNA, and protein expression in activated T lymphocytes. J Immunol2011; 187: 2233–2243.
40.
KumarMAhmadTSharmaA. Let-7 microRNA-mediated regulation of IL-13 and allergic airway inflammation. J Allergy Clin Immunol2011; 128: 1077–1085.
41.
LehmannSMKrugerCParkB. An unconventional role for miRNA: let-7 activates Toll-like receptor 7 and causes neurodegeneration. Nat Neurosci2012; 15: 827–835.
42.
RoushSSlackFJ. The let-7 family of microRNAs. Trends Cell Biol2008; 18: 505–516.
43.
SwaminathanSSuzukiKSeddikiN. Differential regulation of the Let-7 family of microRNAs in CD4+ T cells alters IL-10 expression. J Immunol2012; 188: 6238–6246.
44.
HaghikiaAHaghikiaAHellwigK. Regulated microRNAs in the CSF of patients with multiple sclerosis: a case-control study. Neurology2012; 79: 2166–2170.
45.
MinagarA. Current and future therapies for multiple sclerosis. Scientifica2013; 2013: 249101.
46.
ComabellaMLunemannJDRioJ. A type I interferon signature in monocytes is associated with poor response to interferon-beta in multiple sclerosis. Brain2009; 132: 3353–3365.
47.
RudickRARaniMRXuY. Excessive biologic response to IFNbeta is associated with poor treatment response in patients with multiple sclerosis. PLoS One2011; 6: e19262.
48.
SieversCMeiraMHoffmannF. Altered microRNA expression in B lymphocytes in multiple sclerosis: towards a better understanding of treatment effects. Clin Immunol2012; 144: 70–79.
49.
VenturaAYoungAGWinslowMM. Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell2008; 132: 875–886.
50.
HeckerMThamilarasanMKoczanD. MicroRNA expression changes during interferon-beta treatment in the peripheral blood of multiple sclerosis patients. Int J Mol Sci2013; 14: 16087–16110.
51.
KrohEMParkinRKMitchellPS. Analysis of circulating microRNA biomarkers in plasma and serum using quantitative reverse transcription-PCR (qRT-PCR). Methods2010; 50: 298–301.