Abstract
Long non-coding RNAs (lncRNAs) play critical roles in regulation of immunological pathways. Consequently, their expression profile represents new biomarkers for susceptibility and progression of immunological disorders. However, their role in chronic inflammatory diseases such as multiple sclerosis (MS) remained unknown. Here, we assessed the expression of lncRNAs MALAT1 and HOTAIRM1 as well as their target genes in peripheral blood of MS patients to show their possible roles in disease initiation and progression. In this study, 50 patients with relapsing-remitting MS and 50 healthy matched controls were enrolled. Comparative Ct method via TaqMan assay was used to quantify transcript levels of MALAT1, HOTAIRM1, AGO2, CSTF2, CPSF7, and WDR33. Our analysis depicted significant differences in lncRNAs and their target genes expression levels. AGO2 expression was significantly elevated in MS patients (P < 0.001) whereas, CSTF2 expiration was considerably down-regulated (P < 0.042). These findings suggest that AGO2 and CSTF2 can be considered as potential theoretical biomarkers for MS and can be helpful for diagnosis and prognosis of responding patients to interferon.
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References
Atianand MK, Fitzgerald KA (2014) Long non-coding RNAs and control of gene expression in the immune system. Trends Mol Med 20:623–631
Chan SL, Huppertz I, Yao C, Weng L, Moresco JJ, Yates JR 3rd, Ule J, Manley JL, Shi Y (2014) CPSF30 and Wdr33 directly bind to AAUAAA in mammalian mRNA 3' processing. Genes Dev 28:2370–2380
Chen Z-H, Wang W-T, Huang W, Fang K, Sun Y-M, Liu S-R, Luo X-Q, Chen Y-Q (2017) The lncRNA HOTAIRM1 regulates the degradation of PML-RARA oncoprotein and myeloid cell differentiation by enhancing the autophagy pathway. Cell Death Differ 24:212–224
Chuvpilo S, Zimmer M, Kerstan A, Glöckner J, Avots A, Escher C, Fischer C, Inashkina I, Jankevics E, Berberich-Siebelt F (1999) Alternative polyadenylation events contribute to the induction of NF-ATc in effector T cells. Immunity 10:261–269
Compston A, Coles A (2008) Multiple sclerosis. Lancet 372:1502–1517
Curinha A, Oliveira Braz S, Pereira-Castro I, Cruz A, Moreira A (2014) Implications of polyadenylation in health and disease. Nucleus 5:508–519
Eftekharian MM, Ghannad MS, Taheri M, Roshanaei G, Mazdeh M, Musavi M, Hormoz MB (2016) Frequency of viral infections and environmental factors in multiple sclerosis. Hum Antibodies 24:17–23
Eftekharian MM, Ghafouri-Fard S, Soudyab M, Omrani MD, Rahimi M, Sayad A, Komaki A, Mazdeh M, Taheri M (2017) Expression analysis of long non-coding RNAs in the blood of multiple sclerosis patients. J Mol Neurosci 63:333–341
Fenoglio C, Calvi A, Serpente M, De Riz M, Comi C, Lecchi E, Pietroboni A, Arcaro M, Cioffi S, Oldoni E (2016) Long non coding RNA (LncRNAs) expression analysis in patients with multiple sclerosis: potential biomarkers of disease susceptibility and progression. Mult Scler J. SAGE Publications Ltd 1 Olivers Yard, 55 City Road, London EC1Y 1SP, England, p 271
Gutschner T, Hämmerle M, Eißmann M, Hsu J, Kim Y, Hung G, Revenko A, Arun G, Stentrup M, Groß M (2013) The noncoding RNA MALAT1 is a critical regulator of the metastasis phenotype of lung cancer cells. Cancer Res 73:1180–1189
Harbo HF, Gold R, Tintore M (2013) Sex and gender issues in multiple sclerosis. Ther Adv Neurol Disord 6:237–248
Hatami M, Salmani T, Arsang-Jang S, Davood Omrani M, Mazdeh M, Ghafouri-Fard S, Sayad A, Taheri M (2018) STAT5a and STAT6 gene expression levels in multiple sclerosis patients. Cytokine 106:108–113
Kondrashov A, Meijer HA, Barthet-Barateig A, Parker HN, Khurshid A, Tessier S, Sicard M, Knox AJ, Pang L, De Moor CH (2012) Inhibition of polyadenylation reduces inflammatory gene induction. Rna 18:2236–2250
Leucci E, Patella F, Waage J, Holmstrøm K, Lindow M, Porse B, Kauppinen S, Lund AH (2013) microRNA-9 targets the long non-coding RNA MALAT1 for degradation in the nucleus. Sci Rep 3:2535
Li C, Chen J, Zhang K, Feng B, Wang R, Chen L (2015) Progress and prospects of long noncoding RNAs (lncRNAs) in hepatocellular carcinoma. Cell Physiol Biochem 36:423–434
Nunez-Iglesias J, Liu CC, Morgan TE, Finch CE, Zhou XJ (2010) Joint genome-wide profiling of miRNA and mRNA expression in Alzheimer’s disease cortex reveals altered miRNA regulation. PLoS One 5:e8898
Pearson MJ, Jones SW (2016) Long noncoding RNAs in the regulation of inflammatory pathways in rheumatoid arthritis and osteoarthritis. Arthritis Rheumatol 68:2575–2583
Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69:292–302
Rezazadeh M, Gharesouran J, Moradi M, Noroozi R, Omrani MD, Taheri M, Ghafouri-Fard S (2018) Association study of ANRIL genetic variants and multiple sclerosis. J Mol Neurosci:1–6
Schönemann L, Kühn U, Martin G, Schäfer P, Gruber AR, Keller W, Zavolan M, Wahle E (2014) Reconstitution of CPSF active in polyadenylation: recognition of the polyadenylation signal by WDR33. Genes Dev 28:2381–2393
Taheri M, Ghafouri-Fard S, Solgi G, Sayad A, Mazdeh M, Omrani MD (2017) Determination of cytokine levels in multiple sclerosis patients and their relevance with patients’ response to Cinnovex. Cytokine 96:138–143
Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3:research0034. 1
Wang L-Q, Zhou H-J (2018) LncRNA MALAT1 promotes high glucose-induced inflammatory response of microglial cells via provoking MyD88/IRAK1/TRAF6 signaling. Sci Rep 8:8346
Wang X, Li M, Wang Z, Han S, Tang X, Ge Y, Zhou L, Zhou C, Yuan Q, Yang M (2015) Silencing of long noncoding RNA MALAT1 by miR-101 and miR-217 inhibits proliferation, migration, and invasion of esophageal squamous cell carcinoma cells. J Biol Chem 290:3925–3935
Wu P, Zuo X, Deng H, Liu X, Liu L, Ji A (2013) Roles of long noncoding RNAs in brain development, functional diversification and neurodegenerative diseases. Brain Res Bull 97:69–80
Yao C, Biesinger J, Wan J, Weng L, Xing Y, Xie X, Shi Y (2012) Transcriptome-wide analyses of CstF64–RNA interactions in global regulation of mRNA alternative polyadenylation. Proc Natl Acad Sci 109:18773–18778
Yao J, Wang XQ, Li YJ, Shan K, Yang H, Yao MD, Liu C, Li XM, Shen Y, Liu JY (2016) Long non-coding RNA MALAT1 regulates retinal neurodegeneration through CREB signaling. EMBO Mol Med e201505725
Zhou HJ, Wang LQ, Xu QS, Fan ZX, Zhu Y, Jiang H, Zheng XJ, Ma YH, Zhan RY (2016) Downregulation of miR-199b promotes the acute spinal cord injury through IKKbeta-NF-kappaB signaling pathway activating microglial cells. Exp Cell Res 349:60–67
Acknowledgments
We thank our patients for participating in this study. This article has been extracted from thesis written by Jalal Gharesouran in Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran (registration no; 3).
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This work was financially supported by a grant allocated by the Deputy of Research, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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Gharesouran, J., Taheri, M., Sayad, A. et al. A Novel Regulatory Function of Long Non-coding RNAs at Different Levels of Gene Expression in Multiple Sclerosis. J Mol Neurosci 67, 434–440 (2019). https://doi.org/10.1007/s12031-018-1248-2
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DOI: https://doi.org/10.1007/s12031-018-1248-2