Skip to main content
SpringerLink
Log in

Under-expression of microRNA-146a and 21 and their association with Crohn’s disease

  • Short Report
  • Published:
Indian Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

MicroRNAs (miRNAs) can post-transcriptionally regulate gene expression and are involved in the immune response. Excessive immune response to the gut microbiota plays a major role in the pathogenesis of Crohn’s disease (CD). Regarding the role of miRNAs in immune response, this study aimed to investigate the contribution of miRNAs in the pathogenesis of CD. A total of 53 participants, including 23 CD patients and 30 healthy controls (HCs) were enrolled in this study. miRNAs, including miR-21, miR-29a, miR-29b, miR-31, miR-146a, miR-155, miR-181a, and miR-181c were evaluated via TaqMan MicroRNA Assays. Among the eight miRNAs, the amounts of miR-146a and miR-21 were significantly decreased in the CD patients relative to HC subjects. Moreover, we showed that there was a negative correlation between miR-146a and Harvey-Bradshaw index (HBI), as well as a positive correlation of miR-21 and miR-29b with HBI. Under-expression of miR-146a and miR-21, which are critical for the regulatory function of regulatory T cells (Tregs), is remarkably associated with CD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

References

  1. GBD 2017 Inflammatory Bowel Disease Collaborators. The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2020;5:17–30.

  2. Khalili A, Ebrahimpour S, Maleki I, Abediankenari S, Afrouzi MA. CD4+ CD25+ CD127low FoxP3+ regulatory T cells in Crohn’s disease. Rom J Intern Med. 2018;56:158–66.

  3. Jensen MD, Andersen RF, Christensen H, Nathan T, Kjeldsen J, Madsen JS. Circulating microRNAs as biomarkers of adult Crohn’s disease. Eur J Gastroenterol Hepatol. 2015;27:1038–44.

    Article  CAS  PubMed  Google Scholar 

  4. Ji Y, Li X, Zhu Y, Li N, Zhang N, Niu M. Faecal microRNA as a biomarker of the activity and prognosis of inflammatory bowel diseases. Biochem Biophys Res Commun. 2018;503:2443–50.

    Article  CAS  PubMed  Google Scholar 

  5. Zhao H, Chen J, Chen J, et al. miR-192/215-5p act as tumor suppressors and link Crohn’s disease and colorectal cancer by targeting common metabolic pathways: an integrated informatics analysis and experimental study. J Cell Physiol. 2019;234:21060–75.

    Article  CAS  PubMed  Google Scholar 

  6. Tehrani SS, Karimian  A, Parsian  H, Majidinia M, Yousefi B. Multiple functions of long non-coding RNAs in oxidative stress, DNA damage response and cancer progression. J Cell Biochem. 2018;119:223–36.

  7. Maniati  MS, Maniati M, Yousefi T, Ahmadi-Ahangar A, Tehrani SS. New insights into the role of microRNAs and long noncoding RNAs in most common neurodegenerative diseases. J Cell Biochem. 2019;120:8908–18.

  8. Mirhosseini SA, Sarfi M, Tehrani SS, Mirazakhani  M, Maniati  M, Amani  J. Modulation of cancer cell signaling by long noncoding RNAs. J Cell Biochem. 2019;120:12224–46.

  9. Peck BC, Weiser M, Lee SE, et al. MicroRNAs classify different disease behavior phenotypes of Crohn’s disease and may have prognostic utility. Inflamm Bowel Dis. 2015;21:2178–87.

  10. Vahed SZ, Zonouzi AP, Ghanbarian H, et al. Differential expression of circulating miR-21, miR-142-3p and miR-155 in renal transplant recipients with impaired graft function. Int Urol Nephrol. 2017;49:1681–9.

  11. Zhang Y, Chen J, Xue Q, et al. Prognostic significance of microRNAs in glioma: a systematic review and meta-analysis. Biomed Res Int. 2019;2019:4015969.

    PubMed Central  PubMed  Google Scholar 

  12. Mohammadnia-Afrouzi M, Hosseini AZ, Khalili A, et al. Altered microRNA expression and immunosuppressive cytokine production by regulatory T cells of ulcerative colitis patients. Immunol Invest. 2016;45:63–74.

  13. Soltanzadeh-Yamchi M, Shahbazi M, Aslani S, Mohammadnia-Afrouzi M. MicroRNA signature of regulatory T cells in health and autoimmunity. Biomed Pharmacother. 2018;100:316–23.

    Article  CAS  PubMed  Google Scholar 

  14. Rojas-Feria M, Romero-García T, Caballero-Rico JÁF, et al. Modulation of faecal metagenome in Crohn’s disease: role of microRNAs as biomarkers. World J Gastroenterol. 2018;24:5223–33.

  15. Cao B, Zhou X, Ma J, et al. Role of MiRNAs in inflammatory bowel disease. Dig Dis Sci. 2017;62:1426–38.

  16. Verstockt S, De Hertogh G, Van der Goten J, et al. Gene and miRNA regulatory networks during different stages of Crohn’s disease. J Crohn’s Colitis. 2019;13:916–30.

  17. Felwick RK, Dingley GJR, Martinez-Nunez R, Sanchez-Elsner T, Cummings JRF, Collins JE. MicroRNA23a overexpression in Crohn’s disease targets tumour necrosis factor alpha inhibitor protein 3, increasing sensitivity to TNF and modifying the epithelial barrier. J Crohn’s Colitis. 2020;14:381–92.

  18. Xiao C, Rajewsky K. MicroRNA control in the immune system: basic principles. Cell. 2009;136:26–36.

    Article  CAS  PubMed  Google Scholar 

  19. Cobb BS, Hertweck A, Smith J, et al. A role for dicer in immune regulation. J Exp Med. 2006;203:2519–27.

  20. Harvey RF, Bradshaw JM. A simple index of Crohn’s-disease activity. Lancet. 1980;1:514.

  21. Rossi RL, Rossetti G, Wenandy L, et al. Distinct microRNA signatures in human lymphocyte subsets and enforcement of the naive state in CD4+ T cells by the microRNA miR-125b. Nat Immunol. 2011;12:796–803.

  22. Lu L-F, Boldin MP, Chaudhry A, et al. Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses. Cell. 2010;142:914–29.

  23. Moret-Tatay I, Iborra M, Cerrillo E, Tortosa L, Nos P, Beltrán B. Possible biomarkers in blood for Crohn’s disease: oxidative stress and microRNAs—current evidences and further aspects to unravel. Oxid Med Cell Longev. 2016;2016:2325162. 

  24. Tang Y, Luo X, Cui H, et al. MicroRNA-146a contributes to abnormal activation of the type I interferon pathway in human lupus by targeting the key signaling proteins.Arthritis Rheum. 2009;60:1065–75.

  25. Szűcs D, Béres NJ, Rokonay R, et al. Increased duodenal expression of miR-146a and-155 in pediatric Crohn’s disease. World J Gastroenterol. 2016;22:6027–35.

  26. Schaefer JS, Attumi T, Opekun AR, et al. MicroRNA signatures differentiate Crohn’s disease from ulcerative colitis. BMC Immunol. 2015;16:5.

  27. Rouas R, Fayyad-Kazan H, El Zein N, et al. Human natural Treg microRNA signature: role of microRNA-31 and microRNA-21 in FOXP3 expression. Eur J Immunol. 2009;39:1608–18.

  28. Namdari H, Ghayedi M, Hadjati J, et al. Effect of MicroRNA-21 transfection on in-vitro differentiation of human naive CD4+ T cells to regulatory T cells. Iran J Allergy Asthma Immunol. 2017;16:235–44.

  29. Carissimi C, Carucci N, Colombo T, et al. miR-21 is a negative modulator of T-cell activation. Biochimie. 2014;107:319–26.

Download references

Author information

Authors and Affiliations

  1. Student Research Committee, School of Medicine, Babol University of Medical Sciences, Babol, Iran

    Mohammad Mirzakhani

  2. Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Ganjafrooz Street, Babol, IR, Iran

    Mohammad Mirzakhani, Mehdi Shahbazi & Mousa Mohammadnia-Afrouzi

  3. Immunoregulation Research Center, Health Research Institute, Babol University of Medical Sciences, Ganjafrooz Street, Babol, IR, Iran

    Mohammad Mirzakhani, Mehdi Shahbazi & Mousa Mohammadnia-Afrouzi

  4. Immunogenetics Research Center, Mazandaran University of Medical Sciences, Sari, IR, Iran

    Ali Khalili & Saeid Abediankenari

  5. Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran

    Soheil Ebrahimpour

  6. Department of Immunology, School of Medicine, Babol University of Medical Sciences, Ganjafrooz Street, Babol, IR, Iran

    Mousa Mohammadnia-Afrouzi

Authors
  1. Mohammad Mirzakhani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ali Khalili
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mehdi Shahbazi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Saeid Abediankenari
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Soheil Ebrahimpour
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mousa Mohammadnia-Afrouzi
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Experimental work was carried out by MM, AK, MS, and SE. SA and MMA had an advisory role. All authors contributed to the manuscript writing and had input into reviewing the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Mousa Mohammadnia-Afrouzi.

Ethics declarations

Conflict of interest

MM, AK, MS, SA, SE, and MMA declare that they have no conflict of interest.

Ethics statement

The study was performed conforming to the Helsinki declaration of 1975, as revised in 2000 and 2008 concerning human and animal rights, and the authors followed the policy concerning informed consent as shown on Springer.com.

Disclaimer

The authors are solely responsible for the data and the contents of the paper. In no way, the Honorary Editor-in-Chief, Editorial Board Members, or the printer/publishers are responsible for the results/findings and content of this article.

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

Mirzakhani, M., Khalili, A., Shahbazi, M. et al. Under-expression of microRNA-146a and 21 and their association with Crohn’s disease. Indian J Gastroenterol 39, 405–410 (2020). https://doi.org/10.1007/s12664-020-01059-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12664-020-01059-2

Keywords

Search

Navigation