Skip to main content

Advertisement

Log in

Micro-organic basis of functional gastrointestinal (GI) disorders: Role of microRNAs in GI pacemaking cells

  • Technical Notes
  • Published:
Indian Journal of Gastroenterology Aims and scope Submit manuscript

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

Access this article

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

Instant access to the full article PDF.

Fig. 1

References

  1. Black CJ, Drossman DA, Talley NJ, Ruddy J, Ford AC. Functional gastrointestinal disorders: advances in understanding and management. Lancet. 2020;396:1664–74.

    Article  CAS  PubMed  Google Scholar 

  2. Sperber AD, Bangdiwala SI, Drossman DA, et al. Worldwide prevalence and burden of functional gastrointestinal disorders, results of Rome Foundation Global Study. Gastroenterology. 2021;160:99–114. e3.

    Article  PubMed  Google Scholar 

  3. Ford AC, Mahadeva S, Carbone MF, Lacy BE, Talley NJ. Functional dyspepsia. Lancet. 2020;396:1689–702.

    Article  CAS  PubMed  Google Scholar 

  4. Ghoshal UC. Marshall and Warren Lecture 2019: A paradigm shift in pathophysiological basis of irritable bowel syndrome and its implication on treatment. J Gastroenterol Hepatol. 2020;35:712–21.

    Article  CAS  PubMed  Google Scholar 

  5. Grover M, Farrugia G, Stanghellini V. Gastroparesis: a turning point in understanding and treatment. Gut. 2019;68:2238–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ford AC, Sperber AD, Corsetti M, Camilleri M. Irritable bowel syndrome. Lancet. 2020;396:1675–88.

    Article  CAS  PubMed  Google Scholar 

  7. Sanders KM, Koh SD, Ro S, Ward SM. Regulation of gastrointestinal motility--insights from smooth muscle biology. Nat Rev Gastroenterol Hepatol. 2012;9:633–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Mazzone A, Strege PR, Gibbons SJ, et al. microRNA overexpression in slow transit constipation leads to reduced NaV1.5 current and altered smooth muscle contractility. Gut. 2020;69:868–76.

    Article  PubMed  Google Scholar 

  9. Vicario M, Martinez C, Santos J. Role of microRNA in IBS with increased gut permeability. Gut. 2010;59:710–2.

    Article  CAS  PubMed  Google Scholar 

  10. Michaels YS, Barnkob MB, Barbosa H, et al. Precise tuning of gene expression levels in mammalian cells. Nat Commun. 2019;10:818.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. McGeary SE, Lin KS, Shi CY, et al. The biochemical basis of microRNA targeting efficacy. Science. 2019;366:eaav1741.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Dragomir MP, Knutsen E, Calin GA. SnapShot: unconventional miRNA functions. Cell. 2018;174:1038–e1.

    Article  CAS  PubMed  Google Scholar 

  13. Catalanotto C, Cogoni C, Zardo G. MicroRNA in control of gene expression: an overview of nuclear functions. Int J Mol Sci. 2016;17:1712.

  14. Park C, Hennig GW, Sanders KM, et al. Serum response factor-dependent MicroRNAs regulate gastrointestinal smooth muscle cell phenotypes. Gastroenterology. 2011;141:164–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Yu C, Zang L, Feng B, et al. Coexpression network analysis identified specific miRNAs and genes in association with slowtransit constipation. Mol Med Rep. 2020;22:4696–706.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Nezami BG, Mwangi SM, Lee JE, et al. MicroRNA 375 mediates palmitate-induced enteric neuronal damage and high-fat diet-induced delayed intestinal transit in mice. Gastroenterology. 2014;146:473–83 e3.

    Article  CAS  PubMed  Google Scholar 

  17. Zhou Q, Yang L, Larson S, et al. Decreased miR-199 augments visceral pain in patients with IBS through translational upregulation of TRPV1. Gut. 2016;65:797–805.

    Article  CAS  PubMed  Google Scholar 

  18. Wouters MM. Novel insight in diarrhoea-predominant IBS: miRNAs modulate barrier function. Gut. 2017;66:1537–8.

    Article  CAS  PubMed  Google Scholar 

  19. Zhou Q, Souba WW, Croce CM, Verne GN. MicroRNA-29a regulates intestinal membrane permeability in patients with irritable bowel syndrome. Gut. 2010;59:775–84.

    Article  CAS  PubMed  Google Scholar 

  20. Zang H, Liu Y, Chen Z, Fan G. miR-222 regulates cell growth, apoptosis, and autophagy of interstitial cells of Cajal isolated from slow transit constipation rats by targeting c-kit. Indian J Gastroenterol. 2021;40. https://doi.org/10.1007/s12664-020-01143-7.

  21. Deng JJ, Lai MY, Tan X, Yuan Q. Acupuncture protects the interstitial cells of Cajal by regulating miR-222 in a rat model of post-operative ileus. Acupunct Med. 2019;37:125–32.

    Article  PubMed  Google Scholar 

  22. Ke HJ, Li J, Yang XJ, et al. miR-551b-5p increases intracellular Ca(2+) concentration but does not alter c-Kit expression in rat interstitial cells of Cajal. Int J Clin Exp Pathol. 2017;10:7578–85.

    PubMed  PubMed Central  Google Scholar 

  23. Park C, Lee MY, Slivano OJ, et al. Loss of serum response factor induces microRNA-mediated apoptosis in intestinal smooth muscle cells. Cell Death Dis. 2015;6:e2011.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Liu W, Zhang Q, Li S, et al. The relationship between colonic macrophages and MicroRNA-128 in the pathogenesis of slow transit constipation. Dig Dis Sci. 2015;60:2304–15.

    Article  CAS  PubMed  Google Scholar 

  25. Ren HX, Zhang FC, Luo HS, Zhang G, Liang LX. Role of mast cell-miR-490-5p in irritable bowel syndrome. World J Gastroenterol. 2017;23:93–102.  

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Wohlfarth C, Schmitteckert S, Hartle JD, et al. miR-16 and miR-103 impact 5-HT4 receptor signalling and correlate with symptom profile in irritable bowel syndrome. Sci Rep. 2017;7:14680.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Kapeller J, Houghton LA, Monnikes H, et al. First evidence for an association of a functional variant in the microRNA-510 target site of the serotonin receptor-type 3E gene with diarrhea predominant irritable bowel syndrome. Hum Mol Genet. 2008;17:2967–77.

    Article  CAS  PubMed  Google Scholar 

  28. Liao XJ, Mao WM, Wang Q, Yang GG, Wu WJ, Shao SX. MicroRNA-24 inhibits serotonin reuptake transporter expression and aggravates irritable bowel syndrome. Biochem Biophys Res Commun. 2016;469:288–93. 

    Article  CAS  PubMed  Google Scholar 

  29. Zhu H, Xiao X, Shi Y, et al. Inhibition of miRNA-29a regulates intestinal barrier function in diarrhea-predominant irritable bowel syndrome by upregulating ZO-1 and CLDN1. Exp Ther Med. 2020;20:155.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Cichon C, Sabharwal H, Ruter C, Schmidt MA. MicroRNAs regulate tight junction proteins and modulate epithelial/endothelial barrier functions. Tissue Barriers. 2014;2:e944446.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Fei L, Wang Y. microRNA-495 reduces visceral sensitivity in mice with diarrhea-predominant irritable bowel syndrome through suppression of the PI3K/AKT signaling pathway via PKIB. IUBMB Life. 2020;72:1468–80.

    Article  CAS  PubMed  Google Scholar 

  32. Hou Q, Huang Y, Zhang C, et al. MicroRNA-200a targets Cannabinoid Receptor 1 and serotonin transporter to increase visceral hyperalgesia in diarrhea-predominant irritable bowel syndrome rats. J Neurogastroenterol Motil. 2018;24:656–68.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Karnati HK, Panigrahi MK, Gutti RK, Greig NH, Tamargo IA. miRNAs: key players in neurodegenerative disorders and epilepsy. J Alzheimers Dis. 2015;48:563–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Mawe GM, Hoffman JM. Serotonin signalling in the gut--functions, dysfunctions and therapeutic targets. Nat Rev Gastroenterol Hepatol. 2013;10:473–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Barbara G, Feinle-Bisset C, Ghoshal UC,  et al. The intestinal microenvironment and functional gastrointestinal disorders. Gastroenterology. 2016;S0016-5085(16)00219-5. https://doi.org/10.1053/j.gastro.2016.02.028.

  36. O’Connell RM, Rao DS, Chaudhuri AA, Baltimore D. Physiological and pathological roles for microRNAs in the immune system. Nat Rev Immunol. 2010;10:111–22.

    Article  PubMed  Google Scholar 

  37. Kalla R, Ventham NT, Kennedy NA, et al. MicroRNAs: new players in IBD. Gut. 2015;64:504–17.

    Article  CAS  PubMed  Google Scholar 

  38. Hirschberger S, Hinske LC, Kreth S. MiRNAs: dynamic regulators of immune cell functions in inflammation and cancer. Cancer Lett. 2018;431:11–21.

    Article  CAS  PubMed  Google Scholar 

  39. Boldin MP, Taganov KD, Rao DS, et al. miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice. J Exp Med. 2011;208:1189–201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Androulidaki A, Iliopoulos D, Arranz A, et al. The kinase Akt1 controls macrophage response to lipopolysaccharide by regulating microRNAs. Immunity. 2009;31:220–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Chen XM, Splinter PL, O'Hara SP, LaRusso NF. A cellular micro-RNA, let-7i, regulates Toll-like receptor 4 expression and contributes to cholangiocyte immune responses against Cryptosporidium parvum infection. J Biol Chem. 2007;282:28929–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Rodriguez A, Vigorito E, Clare S, et al. Requirement of bic/microRNA-155 for normal immune function. Science. 2007;316:608–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Farzaei MH, Bahramsoltani R, Abdollahi M, Rahimi R. The role of visceral hypersensitivity in irritable bowel syndrome: pharmacological targets and novel treatments. J Neurogastroenterol Motil. 2016;22:558–74.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Tanaka F, Takashima S, Nadatani Y, et al. Exosomal hsa-miR-933 in gastric juice as a potential biomarker for functional dyspepsia. Dig Dis Sci. 2020;65:3493–501.

    Article  CAS  PubMed  Google Scholar 

  45. Deng Y, Zhou X, Xiang X, Ou Y, He J.  Effect of miRNA-19a on gastrointestinal motility in rats with functional dyspepsia. Exp Ther Med. 2018;15:4875–9.

    PubMed  PubMed Central  Google Scholar 

  46. Arisawa T, Tahara T, Fukuyama T, et al. Genetic polymorphism of pri-microRNA 325, targeting SLC6A4 3′-UTR, is closely associated with the risk of functional dyspepsia in Japan. J Gastroenterol. 2012;47:1091–8.

    Article  CAS  PubMed  Google Scholar 

  47. Fourie NH, Peace RM, Abey SK, et al. Elevated circulating miR-150 and miR-342-3p in patients with irritable bowel syndrome. Exp Mol Pathol. 2014;96:422–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Zhou Q, Verne GN. miRNA-based therapies for the irritable bowel syndrome. Expert Opin Biol Ther. 2011;11:991–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Zhao S, Chen Q, Kang X, Kong B, Wang Z. Aberrantly expressed genes and miRNAs in slow transit constipation based on RNA-Seq analysis. Biomed Res Int. 2018;2018:2617432.

  50. Bonneau E, Neveu B, Kostantin E, Tsongalis GJ, De Guire V.  How close are miRNAs from clinical practice? A perspective on the diagnostic and therapeutic market. EJIFCC. 2019;30:114–27.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Rupaimoole R, Slack FJ. MicroRNA therapeutics: towards a new era for the management of cancer and other diseases. Nat Rev Drug Discov. 2017;16:203–22.

    Article  CAS  PubMed  Google Scholar 

  52. Bader AG, Brown D, Winkler M. The promise of microRNA replacement therapy. Cancer Res. 2010;70:7027–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Theil K, Imami K, Rajewsky N. Identification of proteins and miRNAs that specifically bind an mRNA in vivo. Nat Commun. 2019;10:4205.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Riffo-Campos AL, Riquelme I, Brebi-Mieville P. Tools for sequence-based miRNA target prediction: what to choose? Int J Mol Sci. 2016;17.

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Uday C. Ghoshal.

Ethics declarations

Conflict of interest

RS, LW, and UCG declare that they have no conflict of interest.

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, the Indian Society of Gastroenterology 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

Singh, R., Wei, L. & Ghoshal, U.C. Micro-organic basis of functional gastrointestinal (GI) disorders: Role of microRNAs in GI pacemaking cells. Indian J Gastroenterol 40, 102–110 (2021). https://doi.org/10.1007/s12664-021-01159-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12664-021-01159-7

Navigation