Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Dysregulation of long noncoding RNA MEG3 and NLRC5 expressions in patients with relapsing-remitting multiple sclerosis: is there any correlation?

Genes & Immunity volume 22, pages 322–326 (2021)Cite this article

Subjects

Abstract

Long noncoding RNA MEG3 and NLRC5 genes are both involved in the immune system and the regulation of NLRC5 by MEG3 is documented in rheumatoid arthritis. Therefore, we intended to evaluate the association between the expressions of MEG3 and NLRC5 in multiple sclerosis (MS). Forty relapsing and remitting MS (RRMS) patients (20 in each group) and twenty healthy individuals were enrolled. The expression level of MEG3 and NLRC5 was assessed in peripheral blood mononuclear cells. Sub-group analysis demonstrated that the expression level of MEG3 is reduced in the relapse patient group compared to remission and healthy groups (p < 0.001). The expression level of NLRC5 was higher in whole patients compared with healthy controls (p < 0.05). Moreover, a negative correlation was observed between the expression of these two genes (r = −0.73, p < 0.0001). To conclude, our findings showed the dysregulation of MEG3 and NLRC5 expressions in RRMS patients. Also, the converse association of MEG3 and NLRC5 reflects that the role of MEG3 in MS development is probably mediated by modulation of NLRC5.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Ehtesham N, Mosallaei M, Karimzadeh MR, Moradikazerouni H, Sharifi M. microRNAs: key modulators of disease-modifying therapies in multiple sclerosis. Int Rev Immunol. 2020;39:264–79. https://doi.org/10.1080/08830185.2020.1779712.

    Article  CAS  PubMed  Google Scholar 

  2. Lemus HN, Warrington AE, Rodriguez M. Multiple sclerosis: mechanisms of disease and strategies for myelin and axonal repair. Neurol Clin. 2018;36:1–11. https://doi.org/10.1016/j.ncl.2017.08.002.

    Article  PubMed  Google Scholar 

  3. Yao RW, Wang Y, Chen LL. Cellular functions of long noncoding RNAs. Nat Cell Biol. 2019;21:542–51. https://doi.org/10.1038/s41556-019-0311-8.

    Article  CAS  PubMed  Google Scholar 

  4. Statello L, Guo C-J, Chen L-L, Huarte M. Gene regulation by long non-coding RNAs and its biological functions. Nat Rev Mol Cell Biol. 2021;22:96–118. https://doi.org/10.1038/s41580-020-00315-9.

    Article  CAS  PubMed  Google Scholar 

  5. Sigdel KR, Cheng A, Wang Y, Duan L, Zhang Y. The emerging functions of long noncoding RNA in immune cells: autoimmune diseases. J Immunol Res. 2015;2015:848790. https://doi.org/10.1155/2015/848790.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Yang X, Wu Y, Zhang B, Ni B. Noncoding RNAs in multiple sclerosis. Clin Epigenetics. 2018;10:149. https://doi.org/10.1186/s13148-018-0586-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Li QW, Lei W, Chen C, Guo W. Recent advances of long noncoding RNAs involved in the development of multiple sclerosis. Chin J Nat Med. 2020;18:36–46. https://doi.org/10.1016/s1875-5364(20)30003-0.

    Article  PubMed  Google Scholar 

  8. Ghaderian S, Shomali N, Behravesh S, Danbaran GR, Hemmatzadeh M, Aslani S. et al. The emerging role of lncRNAs in multiple sclerosis. J Neuroimmunol. 2020;347:577347. https://doi.org/10.1016/j.jneuroim.2020.577347.

    Article  CAS  PubMed  Google Scholar 

  9. Ghafouri-Fard S, Taheri M. Maternally expressed gene 3 (MEG3): A tumor suppressor long non coding RNA. Biomed Pharmacother. 2019;118:109129. https://doi.org/10.1016/j.biopha.2019.109129.

    Article  CAS  PubMed  Google Scholar 

  10. Moradi MT, Fallahi H, Rahimi Z. Interaction of long noncoding RNA MEG3 with miRNAs: A reciprocal regulation. J Cell Biochem. 2019;120:3339–52. https://doi.org/10.1002/jcb.27604.

    Article  CAS  PubMed  Google Scholar 

  11. Li R, Fang L, Pu Q, Bu H, Zhu P, Chen Z, et al. MEG3-4 is a miRNA decoy that regulates IL-1β abundance to initiate and then limit inflammation to prevent sepsis during lung infection. Sci Signal. 2018;11. https://doi.org/10.1126/scisignal.aao2387.

  12. Wu Y, Shi T, Li J. NLRC5: A paradigm for NLRs in immunological and inflammatory reaction. Cancer Lett. 2019;451:92–9. https://doi.org/10.1016/j.canlet.2019.03.005.

    Article  CAS  PubMed  Google Scholar 

  13. Wang J-Q, Liu Y-R, Xia Q, Chen R-N, Liang J, Xia Q-R. et al. Emerging roles for NLRC5 in immune diseases. Front Pharm. 2019;10:1352. https://doi.org/10.3389/fphar.2019.01352.

    Article  CAS  Google Scholar 

  14. Tang F, Xu Y, Zhao B. NLRC5: new cancer buster?. Mol Biol Rep.2020;47:2265–77. https://doi.org/10.1007/s11033-020-05253-5.

    Article  CAS  PubMed  Google Scholar 

  15. Liu YR, Yang L, Xu QQ, Lu XY, Ma TT, Huang C. et al. Long noncoding RNA MEG3 regulates rheumatoid arthritis by targeting NLRC5. J Cell Physiol. 2019;234:14270–84. https://doi.org/10.1002/jcp.28126.

    Article  CAS  PubMed  Google Scholar 

  16. Wang Q, Li M, Shen Z, Bu F, Yu H, Pan X. et al. The long non-coding RNA MEG3/miR-let-7c-5p axis regulates ethanol-induced hepatic steatosis and apoptosis by targeting NLRC5. Front Pharm. 2018;9:302 https://doi.org/10.3389/fphar.2018.00302.

    Article  CAS  Google Scholar 

  17. Nociti V, Santoro M. What do we know about the role of lncRNAs in multiple sclerosis?. Neural Regen Res. 2021;16:1715–22. https://doi.org/10.4103/1673-5374.306061.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Ghaiad HR, Elmazny AN, Nooh MM, El-Sawalhi MM, Shaheen AA. Long noncoding RNAs APOA1-AS, IFNG-AS1, RMRP and their related biomolecules in Egyptian patients with relapsing-remitting multiple sclerosis: Relation to disease activity and patient disability. J Adv Res. 2020;21:141–50. https://doi.org/10.1016/j.jare.2019.10.012.

    Article  CAS  PubMed  Google Scholar 

  19. Hosseini A, Teimuri S, Ehsani M, Rasa SMM, Etemadifar M, Nasr Esfahani MH. et al. LncRNAs associated with multiple sclerosis expressed in the Th1 cell lineage. J Cell Physiol. 2019;234:22153–62. https://doi.org/10.1002/jcp.28779.

    Article  CAS  PubMed  Google Scholar 

  20. Ganji M, Sayad A, Omrani MD, Arsang-Jang S, Mazdeh M, Taheri M. Expression analysis of long non-coding RNAs and their target genes in multiple sclerosis patients. Neurol Sci. 2019;40:801–11. https://doi.org/10.1007/s10072-019-3720-3.

    Article  PubMed  Google Scholar 

  21. Al-Rugeebah A, Alanazi M, Parine NR. MEG3: an oncogenic long non-coding RNA in different cancers. Pathol Oncol Res. 2019;25:859–74. https://doi.org/10.1007/s12253-019-00614-3.

    Article  CAS  PubMed  Google Scholar 

  22. Li G, Liu Y, Meng F, Xia Z, Wu X, Fang Y. et al. LncRNA MEG3 inhibits rheumatoid arthritis through miR-141 and inactivation of AKT/mTOR signalling pathway. J Cell Mol Med. 2019;23:7116–20. https://doi.org/10.1111/jcmm.14591.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Wahba AS, Ibrahim ME, Mesbah NM, Saleh SM, Abo-Elmatty DM, Mehanna ET. Long non-coding RNA MEG3 and its genetic variant rs941576 are associated with rheumatoid arthritis pathogenesis in Egyptian patients. Arch Physiol Biochem. 2020:1–8. https://doi.org/10.1080/13813455.2020.1784951.

  24. Chatterjee S, Bhattcharjee D, Misra S, Saha A, Bhattacharyya NP, Ghosh A. Increase in MEG3, MALAT1, NEAT1 significantly predicts the clinical parameters in patients with rheumatoid arthritis. Per Med. 2020;17:445–57. https://doi.org/10.2217/pme-2020-0009.

    Article  CAS  PubMed  Google Scholar 

  25. Moradi A, Rahimi Naiini M, Yazdanpanahi N, Tabatabaeian H, Nabatchian F, Baghi M. et al. Evaluation of the expression levels of three long non-coding RNAs in multiple sclerosis. Cell J. 2020;22:165–70. https://doi.org/10.22074/cellj.2020.6555.

    Article  PubMed  Google Scholar 

  26. Safa A, Taheri M, Fallah H, Salmani T, Arsang-Jang S, Ghafouri-Fard S. et al. Downregulation of cancer-associated lncRNAs in peripheral blood of multiple sclerosis patients. J Mol Neurosci. 2020;70:1533–40. https://doi.org/10.1007/s12031-020-01646-0.

    Article  CAS  PubMed  Google Scholar 

  27. Chang W-w, Zhang L, Yao X-m, Chen Y, Zhu L-j, Fang Z-m. et al. Upregulation of long non-coding RNA MEG3 in type 2 diabetes mellitus complicated with vascular disease: a case–control study. Mol Cell Biochem. 2020;473:93–9. https://doi.org/10.1007/s11010-020-03810-x.

    Article  CAS  PubMed  Google Scholar 

  28. Feng Y, Yang C, Yan W. Expression of lncRNA MEG3 in asthma with different phenotypes and its relationship with course of disease. Exp Ther Med. 2020;19:2211–7. https://doi.org/10.3892/etm.2020.8414.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Jia H-Y, Zhang K, Lu W-J, Xu G-W, Zhang J-F, Tang Z-L. LncRNA MEG3 influences the proliferation and apoptosis of psoriasis epidermal cells by targeting miR-21/caspase-8. BMC Mol Cell Biol. 2019;20:46 https://doi.org/10.1186/s12860-019-0229-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Liu W, Huang L, Zhang C, Liu Z. lncRNA MEG3 is downregulated in ankylosing spondylitis and associated with disease activity, hospitalization time and disease duration. Exp Ther Med. 2019;17:291–7. https://doi.org/10.3892/etm.2018.6921.

    Article  CAS  PubMed  Google Scholar 

  31. Chen Y, Li H, Xiao C, Zeng X, Xiao X, Zhou Q. et al. NLRC5: potential novel non-invasive biomarker for predicting and reflecting the progression of IgA nephritis. J Transl Med. 2018;16:317. https://doi.org/10.1186/s12967-018-1694-1.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Yu H, Ding C, Dai S, Sun J, Wang S, Zhang Z. Long noncoding RNA FER1L4 regulates rheumatoid arthritis via targeting NLRC5. Clin Exp Rheumatol. 2020;38:713–23.

    PubMed  Google Scholar 

  33. Dastmalchi R, Ghafouri-Fard S, Omrani MD, Mazdeh M, Sayad A, Taheri M. Dysregulation of long non-coding RNA profile in peripheral blood of multiple sclerosis patients. Mult Scler Relat Disord. 2018;25:219–26. https://doi.org/10.1016/j.msard.2018.07.044.

    Article  PubMed  Google Scholar 

  34. Bahrami T, Taheri M, Omrani MD, Karimipoor M. Associations between genomic variants in lncRNA-TRPM2-AS and lncRNA-HNF1A-AS1 genes and risk of multiple sclerosis. J Mol Neurosci. 2020;70:1050–5. https://doi.org/10.1007/s12031-020-01504-z.

    Article  CAS  PubMed  Google Scholar 

  35. Taheri M, Noroozi R, Sadeghpour S, Omrani MD, Ghafouri-Fard S. The rs4759314 SNP within Hotair lncRNA is associated with risk of multiple sclerosis. Mult Scler Relat Disord. 2020;40:101986 https://doi.org/10.1016/j.msard.2020.101986.

    Article  PubMed  Google Scholar 

  36. Rezazadeh M, Gharesouran J, Moradi M, Noroozi R, Omrani MD, Taheri M. et al. Association study of ANRIL genetic variants and multiple sclerosis. J Mol Neurosci. 2018;65:54–9. https://doi.org/10.1007/s12031-018-1069-3.

    Article  CAS  PubMed  Google Scholar 

  37. McNicholas N, Hutchinson M, McGuigan C, Chataway J. 2017 McDonald diagnostic criteria: a review of the evidence. Mult Scler Relat Disord. 2018;24:48–54. https://doi.org/10.1016/j.msard.2018.05.011.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We would like to appreciate any support provided by Semnan University of Medical Sciences.

Funding

This research was funded by the Semnan University of Medical Sciences, Semnan, Iran

Author information

Authors and Affiliations

  1. Department of Medical Genetics and Immunology, Faculty of Medicine, Urmia University of Medical Sciences, Urmia, Iran

    Shahram Torkamandi

  2. Department of Medical Genetics, Semnan University of Medical Sciences, Semnan, Iran

    Shima Bahrami, Tahereh Ghorashi, Mohammad Dehani & Mohsen Soosanabadi

  3. Medical Nano-Technology & Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Hadi Bayat

  4. Department of Molecular genetics, Faculty of biological sciences, Tarbiat modares university, Tehran, Iran

    Hadi Bayat

  5. Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Hadi Bayat

  6. Deptartment of Pediatric, Semnan University of Medical Sciences, Semnan, Iran

    Seyyed Mohamad Hoseini

  7. Department of Neurology, Imam Khomeini Hospital, Urmia University of Medical Sciences, Urmia, Iran

    Somaye Rezaei

  8. Department of Neurology, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Somaye Rezaei

Authors
  1. Shahram Torkamandi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shima Bahrami
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tahereh Ghorashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mohammad Dehani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hadi Bayat
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Seyyed Mohamad Hoseini
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Somaye Rezaei
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mohsen Soosanabadi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

ST wrote the drafting manuscript. SB and TG edited the final manuscript. MD and HD performed PBMCs isolation, preparation of RNA, cDNA synthesis, and quantitative real-time PCR. SMH and SR carried out families recruitments and are responsible for clinical assessments, and examination. MS critically reviewed and revised the intellectual content of the manuscript. MS also conceived and designed the whole project. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Mohsen Soosanabadi.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Torkamandi, S., Bahrami, S., Ghorashi, T. et al. Dysregulation of long noncoding RNA MEG3 and NLRC5 expressions in patients with relapsing-remitting multiple sclerosis: is there any correlation?. Genes Immun 22, 322–326 (2021). https://doi.org/10.1038/s41435-021-00154-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41435-021-00154-4

This article is cited by

Search

Advanced search

Quick links