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Boroumand, N., Eshaghiyan, A., Behshood, P., Nateghi, B., & Emadi, F. (2019). Increased Circulating miR-10a Levels Associated with Multiple Sclerosis. Research in Molecular Medicine (RMM), 6(4), 59–68. https://doi.org/10.18502/rmm.v6i4.4804
https://doi.org/10.18502/rmm.v6i4.4804
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Niloofar Boroumand
Niloofar Boroumand
Department of Biotechnology, Faculty of Advanced Sciences and Technologies, University of Isfahan, Isfahan, Iran
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Amir Eshaghiyan
Amir Eshaghiyan
Department of Genetics, Arsanjan Branch, Islamic Azad University, Arsanjan, Shiraz, Iran
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Parisa Behshood
Parisa Behshood
Department of Microbiology, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran
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Behnaz Nateghi
Behnaz Nateghi
Department of Biochemistry, Faculty of Science, Nourdanesh Institutions of Higher Education, Meimeh, Isfahan, Iran
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Farzaneh Emadi
Farzaneh Emadi
Department of Biochemistry, Faculty of Science, Nourdanesh Institutions of Higher Education, Meimeh, Isfahan, Iran
Published Date
- Jul 14, 2019
Increased Circulating miR-10a Levels Associated with Multiple Sclerosis
Abstract
Background: Multiple sclerosis (MS) is an autoimmune disease that causes chronic inflammation of the central nervous system. MicroRNAs (miRNAs) are small non-coding RNAs 19–24 nucleotides long, which are differentially expressed in different tissues. The role of miRNAs in MS remains unclear.
Aim: We assessed miR-10a transcript levels in MS patients during recurrence and two months after relapse.
Materials and Methods: In this case-control study, we used real-time PCR to examine miR-10a expression in the peripheral blood mononuclear cells of 60 patients with relapsing-remitting multiple sclerosis (RRMS), 30 during recurrence and 30 two months after relapse, and 30 healthy subjects who were referred to the MS Clinic of Kashani Hospital, Isfahan Province. In silico analysis was also performed on the validated miR- 10a targets using miRTarBase.
Results: miR-10a expression was higher in RRMS patients during recurrence and two months after relapse (p < 0.0001 and p < 0.0001, respectively) than in the healthy subjects. Furthermore, in silico molecular signaling enrichment analysis identified 12 mRNAs as validated miR-10a targets.
Conclusion: The expression of miR-10a was elevated in patients with RRMS compared to healthy subjects, suggesting that miR-10a could be a potential biomarker for RRMS diagnosis.
References
[1] Sospedra M, Martin R. Immunology of multiple sclerosis. Annu Rev Immunol. 2005;23:683-747.
[2] Naghavian R, Ghaedi K, Kiani-Esfahani A, Ganjalikhani-Hakemi M, Etemadifar M, Nasr-Esfahani MH. miR-141 and miR-200a, revelation of new possible players in modulation of Th17/Treg differentiation and pathogenesis of multiple sclerosis. PLOS ONE. 2015;10(5):e0124555.
[3] Zamvil SS, Steinman L. The T lymphocyte in experimental allergic encephalomyelitis. Annu Rev Immunol. 1990;8(1):579-621.
[4] Etemadifar M, Abtahi SH, Akbari M, Murray RT, Ramagopalan SV, Fereidan-Esfahani M. Multiple sclerosis in Isfahan, Iran: an update. Mult Scler. 2014;20(8):1145-7.
[5] Galetta KM, Bhattacharyya S. Multiple sclerosis and autoimmune neurology of the central nervous system. Med Clin. 2019;103(2):325-36.
[6] Pelletier D, Hafler DA. Fingolimod for multiple sclerosis. N Engl J Med. 2012;366(4):339-47.
[7] Lesko LJ, Atkinson AJ Jr. Use of biomarkers and surrogate endpoints in drug development and regulatory decision making: criteria, validation, strategies. Annu Rev Pharmacol Toxicol. 2001;41(1):347-66.
[8] Bielekova B, Martin R. Development of biomarkers in multiple sclerosis. Brain. 2004;127(7):1463-78.
[9] Zhang Q, Xu J, Chen Q, Chen X, Zen K, Zhang CY. Selective secretion of microRNA in CNS system. Protein Cell. 2013;4(4):243.
[10] Siegel SR, Mackenzie J, Chaplin G, Jablonski NG, Griffiths L. Circulating microRNAs involved in multiple sclerosis. Mol Biol Rep. 2012;39(5):6219-25.
[11] Keller A, Leidinger P, Lange J, Borries A, Schroers H, Scheffler M et al. Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsingremitting disease from healthy controls. PLOS ONE. 2009;4(10):e7440.
[12] Lund AH. miR-10 in development and cancer. Cell Death Differ. 2010;17(2):209.
[13] Garo LP, Murugaiyan G. Contribution of MicroRNAs to autoimmune diseases. Cellular Mol Life Sci. 2016;73(10):2041-51.
[14] Jeker LT, Zhou X, Gershberg K, de Kouchkovsky D, Morar MM, Stadthagen G et al. MicroRNA 10a marks regulatory T cells. PLOS ONE. 2012;7(5):e36684.
[15] Wu W, He C, Liu C, Cao AT, Xue X, Evans-Marin HL et al. miR-10a inhibits dendritic cell activation and Th1/Th17 cell immune responses in IBD. Gut. 2015;64(11):1755-64.
[16] Ujifuku K, Mitsutake N, Takakura S, Matsuse M, Saenko V, Suzuki K et al. MiR-195, miR-455-3p and miR-10a∗ are implicated in acquired temozolomide resistance in glioblastoma multiforme cells. Cancer Lett. 2010;296(2):241-8.
[17] McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50(1):121-7.
[18] Schmittgen, T.D. and Livak, K.J. Analyzing real-time PCR data by the comparative C T method. Nat Protoc. 2008;3(6):1101.
[19] Dweep H, Gretz N, Sticht C. miRWalk database for miRNA–target interactions. InRNA Mapping. 2014:289-305. Humana Press, New York, NY.
[20] Hsu SD, Lin FM, Wu WY, Liang C, Huang WC, Chan WL et al. miRTarBase: a database curates experimentally validated microRNA–target interactions. Nucleic Acids Res. 2010;39(suppl_1):D163-D169.
[21] Disanto G, Barro C, Benkert P, Naegelin Y, Schädelin S, Giardiello A et al. Serum neurofilament light: a biomarker of neuronal damage in multiple sclerosis. Ann Neurol. 2017;81(6):857-70.
[22] Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017;376(3):221-34.
[23] Vistbakka J, Elovaara I, Lehtimäki T, Hagman S. Circulating microRNAs as biomarkers in progressive multiple sclerosis. Mult Scler. 2017;23(3):403-12.
[24] Regev K, Healy BC, Khalid F, Paul A, Chu R, Tauhid S et al. Association between serum microRNAs and magnetic resonance imaging measures of multiple sclerosis severity. JAMA Neurol. 2017;74(3):275-85.
[25] Simpson LJ, Ansel KM. MicroRNA regulation of lymphocyte tolerance and autoimmunity. J Clin Invest. 2015;125(6):2242-9.
[26] Bar-Or A, Nuttall RK, Duddy M, Alter A, Kim HJ, Ifergan I et al. Analyses of all matrix metalloproteinase members in leukocytes emphasize monocytes as major inflammatory mediators in multiple sclerosis. Brain. 2003;126(12):2738-49.
[27] Liu Y, Zhang Y, Wu H, Li Y, Zhang Y, Liu M et al. miR-10a suppresses colorectal cancer metastasis by modulating the epithelial-to-mesenchymal transition and anoikis. Cell Death Dis. 2017;8(4):e2739.
[28] Faraco G, Cavone L, Chiarugi A. The therapeutic potential of HDAC inhibitors in the treatment of multiple sclerosis. Mol Med. 2011;17(5-6):442-7.
[29] Liang D, Zhen L, Yuan T, Huang J, Deng F, Zhang H et al. miR-10a regulates proliferation of human cardiomyocyte progenitor cells by targeting GATA6. PLOS ONE. 2014;9(7):e103097.
[2] Naghavian R, Ghaedi K, Kiani-Esfahani A, Ganjalikhani-Hakemi M, Etemadifar M, Nasr-Esfahani MH. miR-141 and miR-200a, revelation of new possible players in modulation of Th17/Treg differentiation and pathogenesis of multiple sclerosis. PLOS ONE. 2015;10(5):e0124555.
[3] Zamvil SS, Steinman L. The T lymphocyte in experimental allergic encephalomyelitis. Annu Rev Immunol. 1990;8(1):579-621.
[4] Etemadifar M, Abtahi SH, Akbari M, Murray RT, Ramagopalan SV, Fereidan-Esfahani M. Multiple sclerosis in Isfahan, Iran: an update. Mult Scler. 2014;20(8):1145-7.
[5] Galetta KM, Bhattacharyya S. Multiple sclerosis and autoimmune neurology of the central nervous system. Med Clin. 2019;103(2):325-36.
[6] Pelletier D, Hafler DA. Fingolimod for multiple sclerosis. N Engl J Med. 2012;366(4):339-47.
[7] Lesko LJ, Atkinson AJ Jr. Use of biomarkers and surrogate endpoints in drug development and regulatory decision making: criteria, validation, strategies. Annu Rev Pharmacol Toxicol. 2001;41(1):347-66.
[8] Bielekova B, Martin R. Development of biomarkers in multiple sclerosis. Brain. 2004;127(7):1463-78.
[9] Zhang Q, Xu J, Chen Q, Chen X, Zen K, Zhang CY. Selective secretion of microRNA in CNS system. Protein Cell. 2013;4(4):243.
[10] Siegel SR, Mackenzie J, Chaplin G, Jablonski NG, Griffiths L. Circulating microRNAs involved in multiple sclerosis. Mol Biol Rep. 2012;39(5):6219-25.
[11] Keller A, Leidinger P, Lange J, Borries A, Schroers H, Scheffler M et al. Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsingremitting disease from healthy controls. PLOS ONE. 2009;4(10):e7440.
[12] Lund AH. miR-10 in development and cancer. Cell Death Differ. 2010;17(2):209.
[13] Garo LP, Murugaiyan G. Contribution of MicroRNAs to autoimmune diseases. Cellular Mol Life Sci. 2016;73(10):2041-51.
[14] Jeker LT, Zhou X, Gershberg K, de Kouchkovsky D, Morar MM, Stadthagen G et al. MicroRNA 10a marks regulatory T cells. PLOS ONE. 2012;7(5):e36684.
[15] Wu W, He C, Liu C, Cao AT, Xue X, Evans-Marin HL et al. miR-10a inhibits dendritic cell activation and Th1/Th17 cell immune responses in IBD. Gut. 2015;64(11):1755-64.
[16] Ujifuku K, Mitsutake N, Takakura S, Matsuse M, Saenko V, Suzuki K et al. MiR-195, miR-455-3p and miR-10a∗ are implicated in acquired temozolomide resistance in glioblastoma multiforme cells. Cancer Lett. 2010;296(2):241-8.
[17] McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50(1):121-7.
[18] Schmittgen, T.D. and Livak, K.J. Analyzing real-time PCR data by the comparative C T method. Nat Protoc. 2008;3(6):1101.
[19] Dweep H, Gretz N, Sticht C. miRWalk database for miRNA–target interactions. InRNA Mapping. 2014:289-305. Humana Press, New York, NY.
[20] Hsu SD, Lin FM, Wu WY, Liang C, Huang WC, Chan WL et al. miRTarBase: a database curates experimentally validated microRNA–target interactions. Nucleic Acids Res. 2010;39(suppl_1):D163-D169.
[21] Disanto G, Barro C, Benkert P, Naegelin Y, Schädelin S, Giardiello A et al. Serum neurofilament light: a biomarker of neuronal damage in multiple sclerosis. Ann Neurol. 2017;81(6):857-70.
[22] Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B et al. Ocrelizumab versus interferon beta-1a in relapsing multiple sclerosis. N Engl J Med. 2017;376(3):221-34.
[23] Vistbakka J, Elovaara I, Lehtimäki T, Hagman S. Circulating microRNAs as biomarkers in progressive multiple sclerosis. Mult Scler. 2017;23(3):403-12.
[24] Regev K, Healy BC, Khalid F, Paul A, Chu R, Tauhid S et al. Association between serum microRNAs and magnetic resonance imaging measures of multiple sclerosis severity. JAMA Neurol. 2017;74(3):275-85.
[25] Simpson LJ, Ansel KM. MicroRNA regulation of lymphocyte tolerance and autoimmunity. J Clin Invest. 2015;125(6):2242-9.
[26] Bar-Or A, Nuttall RK, Duddy M, Alter A, Kim HJ, Ifergan I et al. Analyses of all matrix metalloproteinase members in leukocytes emphasize monocytes as major inflammatory mediators in multiple sclerosis. Brain. 2003;126(12):2738-49.
[27] Liu Y, Zhang Y, Wu H, Li Y, Zhang Y, Liu M et al. miR-10a suppresses colorectal cancer metastasis by modulating the epithelial-to-mesenchymal transition and anoikis. Cell Death Dis. 2017;8(4):e2739.
[28] Faraco G, Cavone L, Chiarugi A. The therapeutic potential of HDAC inhibitors in the treatment of multiple sclerosis. Mol Med. 2011;17(5-6):442-7.
[29] Liang D, Zhen L, Yuan T, Huang J, Deng F, Zhang H et al. miR-10a regulates proliferation of human cardiomyocyte progenitor cells by targeting GATA6. PLOS ONE. 2014;9(7):e103097.