Advertisement

Journal of Molecular Neuroscience

, Volume 67, Issue 3, pp 434–440 | Cite as

A Novel Regulatory Function of Long Non-coding RNAs at Different Levels of Gene Expression in Multiple Sclerosis

  • Jalal Gharesouran
  • Mohammad Taheri
  • Arezou Sayad
  • Soudeh Ghafouri-Fard
  • Mehrdokht Mazdeh
  • Mir Davood OmraniEmail author
Article

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.

Keywords

Multiple sclerosis MALAT1 HOTAIRM1 AGO2 CSTF2 CPSF7 WDR33 

Notes

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).

Funding Sources

This work was financially supported by a grant allocated by the Deputy of Research, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

References

  1. Atianand MK, Fitzgerald KA (2014) Long non-coding RNAs and control of gene expression in the immune system. Trends Mol Med 20:623–631CrossRefGoogle Scholar
  2. 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 28:2370–2380CrossRefGoogle Scholar
  3. 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 24:212–224CrossRefGoogle Scholar
  4. 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 10:261–269CrossRefGoogle Scholar
  5. Compston A, Coles A (2008) Multiple sclerosis. Lancet 372:1502–1517CrossRefGoogle Scholar
  6. Curinha A, Oliveira Braz S, Pereira-Castro I, Cruz A, Moreira A (2014) Implications of polyadenylation in health and disease. Nucleus 5:508–519CrossRefGoogle Scholar
  7. 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 24:17–23CrossRefGoogle Scholar
  8. 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 63:333–341CrossRefGoogle Scholar
  9. 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 271Google Scholar
  10. 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 73:1180–1189CrossRefGoogle Scholar
  11. Harbo HF, Gold R, Tintore M (2013) Sex and gender issues in multiple sclerosis. Ther Adv Neurol Disord 6:237–248CrossRefGoogle Scholar
  12. 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 106:108–113CrossRefGoogle Scholar
  13. 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 18:2236–2250CrossRefGoogle Scholar
  14. 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 3:2535CrossRefGoogle Scholar
  15. 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 36:423–434CrossRefGoogle Scholar
  16. 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:e8898CrossRefGoogle Scholar
  17. Pearson MJ, Jones SW (2016) Long noncoding RNAs in the regulation of inflammatory pathways in rheumatoid arthritis and osteoarthritis. Arthritis Rheumatol 68:2575–2583CrossRefGoogle Scholar
  18. 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 69:292–302CrossRefGoogle Scholar
  19. 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:1–6Google Scholar
  20. 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 28:2381–2393CrossRefGoogle Scholar
  21. 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 96:138–143CrossRefGoogle Scholar
  22. 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. 1CrossRefGoogle Scholar
  23. 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 8:8346CrossRefGoogle Scholar
  24. 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 290:3925–3935CrossRefGoogle Scholar
  25. 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 97:69–80CrossRefGoogle Scholar
  26. 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 109:18773–18778CrossRefGoogle Scholar
  27. 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 e201505725Google Scholar
  28. 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 349:60–67CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Medical Genetics, School of MedicineShahid Beheshti University of Medical SciencesTehranIran
  2. 2.Student Research CommitteeShahid Beheshti University of Medical SciencesTehranIran
  3. 3.Neurophysiology Research CenterHamadan University of Medical SciencesHamadanIran
  4. 4.Urogenital Stem Cell Research CenterShahid Beheshti University of Medical SciencesTehranIran

Personalised recommendations