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Expression Analysis of Long Non-coding RNAs in the Blood of Multiple Sclerosis Patients

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Abstract

Multiple sclerosis (MS) is a chronic immune-mediated disorder of the central nervous system (CNS) with multiple genetic and environmental risk factors. Long non-coding RNAs (lncRNAs) have been recently reported to participate in the regulation of immune responses. Consequently, aberrant expression of lncRNAs has been suggested as an underlying cause of MS. In the present study, we evaluated the expression of three lncRNAs with putative roles in the regulation of immune response, namely TNF-α and heterogeneous nuclear ribonucleoprotein L (THRIL), Fas cell surface death receptor- antisense 1 (FAS-AS1), and plasmacytoma variant translocation 1 (PVT1) in circulating blood cells of 50 Iranian relapsing–remitting multiple sclerosis (RRMS) patients compared with healthy subjects by means of quantitative real-time polymerase chain reaction (PCR). We detected a significant downregulation of PVT1 and FAS-AS1 expressions in RRMS patients while a significant upregulation of THRIL in patients compared with controls (P < 0.001). Correlation analyses between lncRNA expression levels and clinical data of MS patients revealed no significant correlation between lncRNAs expression levels and Expanded Disability Status Scale (EDSS), a moderate correlation between PVT1 expression levels and duration of the disorder and no significant correlation between lncRNAs expression levels and age at onset. In addition, we demonstrated correlations between the expression levels of PVT1 and THRIL as well as expression levels of THRIL and FAS-AS1 in RRMS patients. In brief, we have demonstrated dysregulation of three lncRNAs in MS patients. Further studies are needed to explore the exact mechanisms by which these lncRNAs participate in regulation of immune responses.

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References

  • Aune TM, Spurlock CF (2016) Long non-coding RNAs in innate and adaptive immunity. Virus Res 212:146–160

    Article  CAS  PubMed  Google Scholar 

  • Austin PJ, Tsitsiou E, Boardman C, Jones SW, Lindsay MA, Adcock IM, Chung KF, Perry MM (2017) Transcriptional profiling identifies the long noncoding RNA plasmacytoma variant translocation (PVT1) as a novel regulator of the asthmatic phenotype in human airway smooth muscle. J Allergy Clin Immunol 139:780–789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bilinska M, Frydecka I, Podemski R, Gruszka E (2003) Fas expression on T cells and sFas in relapsing-remitting multiple sclerosis. Acta Neurol Scand 107:387–393

    Article  CAS  PubMed  Google Scholar 

  • Colombo, T., Farina, L., Macino, G. & Paci, P. 2015. PVT1: a rising star among oncogenic long noncoding RNAs. Biomed Research International

    Google Scholar 

  • Eftekharian MM, Noroozi R, Sayad A, Sarrafzadeh S, Toghi M, Azimi T, Komaki A, Mazdeh M, Inoko H, Taheri M (2016) RAR-related orphan receptor A (RORA): a new susceptibility gene for multiple sclerosis. J Neurol Sci 369:259–262

    Article  CAS  PubMed  Google Scholar 

  • Gnanaprakasam JNR, Wang RN (2017) MYC in regulating immunity: metabolism and beyond. Genes 8

  • Kalliolias GD, Ivashkiv LB (2016) TNF biology, pathogenic mechanisms and emerging therapeutic strategies. Nature Reviews Rheumatology 12:49–62

    Article  CAS  PubMed  Google Scholar 

  • Li Z, Chao TC, Chang KY, Lin N, Patil VS, Shimizu C, Head SR, Burns JC, Rana TM (2014) The long noncoding RNA THRIL regulates TNFalpha expression through its interaction with hnRNPL. Proc Natl Acad Sci U S A 111:1002–1007

    Article  CAS  PubMed  Google Scholar 

  • Mazdeh M, Taheri M, Sayad A, Bahram S, Omrani MD, Movafagh A, Inoko H, Akbari MT, Noroozi R, Hajilooi M, Solgi G (2016) HLA genes as modifiers of response to IFN-beta-1a therapy in relapsing-remitting multiple sclerosis. Pharmacogenomics 17:489–498

    Article  CAS  PubMed  Google Scholar 

  • Naghavian R, Ghaedi K, Kiani-Esfahani A, Ganjalikhani-Hakemi M, Etemadifar M, Nasr-Esfahani MH (2015) miR-141 and miR-200a, revelation of new possible players in modulation of Th17/Treg differentiation and pathogenesis of multiple sclerosis. PLoS One 10:e0124555

    Article  PubMed  PubMed Central  Google Scholar 

  • Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69:292–302

    Article  PubMed  PubMed Central  Google Scholar 

  • Rinta S, Kuusisto H, Raunio M, Paalavuo R, Levula M, Lehtimaki T, Elovaara I (2008) Apoptosis-related molecules in blood in multiple sclerosis. J Neuroimmunol 205:135–141

    Article  CAS  PubMed  Google Scholar 

  • Robinson WH, Genovese MC, Moreland LW (2001) Demyelinating and neurologic events reported in association with tumor necrosis factor alpha antagonism: by what mechanisms could tumor necrosis factor alpha antagonists improve rheumatoid arthritis but exacerbate multiple sclerosis? Arthritis Rheum 44:1977–1983

    Article  CAS  PubMed  Google Scholar 

  • Sayad, A., Ghafouri-Fard, S., Omrani, M. D., Noroozi, R. & Taheri, M. 2017. Myxovirus resistance protein A (MxA) polymorphism is associated with IFNbeta response in Iranian multiple sclerosis patients. Neurol Sci

    Google Scholar 

  • Sehgal L, Mathur R, Braun FK, Wise JF, Berkova Z, Neelapu S, Kwak LW, Samaniego F (2014) FAS-antisense 1 lncRNA and production of soluble versus membrane Fas in B-cell lymphoma. Leukemia 28:2376–2387

    Article  CAS  PubMed  Google Scholar 

  • Soudyab M, Iranpour M, Ghafouri-Fard S (2016) The role of long non-coding rnas in breast cancer. Arch Iran Med 19:508–517

    PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Zhang F, Gao C, Ma XF, Peng XL, Zhang RX, Kong DX, Simard AR, Hao JW (2016) Expression profile of long noncoding rnas in peripheral blood mononuclear cells from multiple sclerosis patients. Cns Neuroscience & Therapeutics 22:298–305

    Article  CAS  Google Scholar 

  • Zhang Y, Cao XT (2016) Long noncoding RNAs in innate immunity. Cellular & Molecular Immunology 13:138–147

    Article  Google Scholar 

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Funding Information

The current study was supported by a grant from Hamadan University of Medical Sciences (grant number: 9507134138).

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Author notes

  1. Mohammad Mahdi Eftekharian and Soudeh Ghafouri-Fard contributed equally to this work.

Authors and Affiliations

  1. Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran

    Mohammad Mahdi Eftekharian & Alireza Komaki

  2. Department of Medical Genetics, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Soudeh Ghafouri-Fard, Mir Davood Omrani, Mahnoosh Rahimi, Arezou Sayad & Mohammad Taheri

  3. Department of Medical Genetics, Mashhad University of Medical Sciences, Mashhad, Iran

    Mohammad Soudyab

  4. Urogenital Stem Cell Research, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mir Davood Omrani & Mohammad Taheri

  5. Department of Neurology, Hamedan University of Medical Sciences, Hamadan, Iran

    Mehrdokht Mazdeh

Authors
  1. Mohammad Mahdi Eftekharian
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  2. Soudeh Ghafouri-Fard
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  3. Mohammad Soudyab
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  4. Mir Davood Omrani
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  5. Mahnoosh Rahimi
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  7. Alireza Komaki
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  9. Mohammad Taheri
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Correspondence to Mohammad Taheri.

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Eftekharian, M.M., Ghafouri-Fard, S., Soudyab, M. et al. Expression Analysis of Long Non-coding RNAs in the Blood of Multiple Sclerosis Patients. J Mol Neurosci 63, 333–341 (2017). https://doi.org/10.1007/s12031-017-0982-1

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  • DOI: https://doi.org/10.1007/s12031-017-0982-1

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