Differential expression of microRNAs as diagnostic biomarkers in inflammatory bowel disease
Main Article Content
Abstract
Introduction: inflammatory bowel diseases (IBD) - primarily Crohn’s disease (CD) and ulcerative colitis (UC) - are chronic disorders of the gastrointestinal tract characterized by persistent inflammation and immune dysregulation, involving genetic, epigenetic, microbiota-related, and environmental factors. Their diagnosis still relies on invasive methods such as colonoscopy, histology, and serum or fecal biomarkers, which show limitations in specificity and discriminative capacity. This scenario has driven the search for non-invasive tools such as microRNAs, small regulatory RNA fragments with high stability that could accurately differentiate between UC and CD. Objective: to evaluate recent evidence on the differential expression of various microRNAs in IBD and their utility as non-invasive diagnostic biomarkers, comparing them with conventional markers such as fecal calprotectin. Methodology: a narrative review was conducted based on a structured search in BVS, PubMed, Web of Science, and Scopus, using DeCS/MeSH terms related to “MicroRNAs,” “Inflammatory bowel disease,” “Crohn disease,” and “Ulcerative colitis.” Articles published in the last five years, in English or Spanish, evaluating the differential expression of microRNAs in IBD were included. Development: several microRNAs show characteristic expression patterns depending on the pathology. In UC, overexpression of miR-16-5p, miR-21-5p, miR-23a-5p, miR-24-3p, miR-29a-3p, miR-126-3p, miR-195-5p, and let-7f-5p has been reported, whereas miR-192-5p, miR-375-3p, and miR-422b-5p are downregulated (9,10,20). In CD, miR-21-5p, miR-16-5p, miR-155-5p, and miR-223-3p are overexpressed, with reduced levels of miR-192-5p and miR-375-3p. These microRNAs participate in key processes such as inflammation, apoptosis, autophagy, and epithelial barrier regulation, supporting their clinical potential. Moreover, some—such as miR-223 and miR-146b-5p—may surpass traditional biomarkers like fecal calprotectin in sensitivity and specificity. Conclusion: microRNAs represent strong candidates as non-invasive diagnostic biomarkers in IBD due to their biological stability, differential expression between UC and CD, and direct relationship with pathophysiological mechanisms. Although the evidence is promising, standardized clinical studies are still needed to validate their routine use in medical practice. General Area of Study: Clinical laboratory. Specific area of study: Molecular biology. Type of study: Narrative review.
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Flores Ruiz, G. A., & Salazar Garcés, L. F. (2026). Differential expression of microRNAs as diagnostic biomarkers in inflammatory bowel disease. Anatomía Digital, 9(1), 27-59. https://doi.org/10.33262/anatomiadigital.v9i1.3575
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Articulos de revisión bibliográfica
References
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22. Hu W, Fang T, Chen X. Identification of differentially expressed genes and miRNAs for ulcerative colitis using bioinformatics analysis. Frontiers in Genetics [Internet]. 2022 [cited 2025 Sep 13]; 13:914384. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9201719/
23. Onisor D, Brusnic O, Banescu C, Carstea C, Sasaran M, Stoian M, et al. miR-155 and miR-21 as Diagnostic and therapeutic biomarkers for ulcerative colitis: there is still a long way to go. Biomedicines [Internet]. 2024 [cited 2025 Sep 13]; 12(6):1315. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC11201222/
24. Saccon TD, Dhahbi JM, Schneider A, Nunez Lopez YO, Qasem A, Cavalcante MB, et al. Plasma miRNA Profile of Crohn’s disease and rheumatoid arthritis patients. Biology [Internet]. 2022 [cited 2025 Sep 13];11(4):508. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9033111/
25. Soroosh A, Fang K, Hoffman JM, Law IKM, Videlock E, Lokhandwala ZA, et al. Loss of miR-24-3p promotes epithelial cell apoptosis and impairs the recovery from intestinal inflammation. Cell Death & Disease [Internet]. 2021 [cited 2025 Oct 19]; 13(1):8. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC8684555/
26. de Oliveira ECS, Quaglio AEV, Grillo TG, Di Stasi LC, Sassaki LY. MicroRNAs in inflammatory bowel disease: What do we know and what can we expect? World Journal of Gastroenterology [Internet]. 2024 [cited 2025 Oct 18];30(16):2184-2190. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC11056918/
27. Atanassova A, Georgieva U. Circulating miRNA-16 in inflammatory bowel disease and some clinical correlations – a cohort study in Bulgarian patients. European Review for Medical Pharmacological Sciences [Internet]. 2022 [cited 2025 Sep 13]; 26 (17): 6310-6315. Available from: https://www.europeanreview.org/article/29655
28. Alfaifi J, Germain A, Heba AC, Arnone D, Gailly L, Ndiaye NC, et al. Deep Dive into MicroRNAs in inflammatory bowel disease. Inflammatory Bowel Diseases [Internet]. 2023 [cited 2025 Nov 24]; 29(6):986–99. Available from: https://academic.oup.com/ibdjournal/article/29/6/986/6955639
29. Yan H, Zhang X, Xu Y. Aberrant expression of miR-21 in patients with inflammatory bowel disease: a protocol for systematic review and meta-analysis. Medicine [Internet]. 2020 [cited 2025 Oct 25];99(17): e19693. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC7220677/
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31. Soroosh A, Rankin CR, Polytarchou C, Lokhandwala ZA, Patel A, Chang L, et al. miR-24 Is elevated in ulcerative colitis patients and regulates intestinal epithelial barrier function. The American Journal of Pathology [Internet]. 2019 [cited 2025 Nov 9]; 189(9):1763–74. Available from: https://www.sciencedirect.com/science/article/pii/S0002944019300896
32. Mestrovic A, Perkovic N, Bozic D, Kumric M, Vilovic M, Bozic J. Precision medicine in inflammatory bowel disease: a spotlight on emerging molecular biomarkers. Biomedicines [Internet]. 2024 [cited 2025 Sep 13];12(7):1520. Available from: https://pubmed.ncbi.nlm.nih.gov/39062093/
33. Masi L, Capobianco I, Magrì C, Marafini I, Petito V, Scaldaferri F. MicroRNAs as innovative biomarkers for inflammatory bowel disease and prediction of colorectal cancer. International Journal of Molecular Sciences [Internet]. 2022 [cited 2025 Oct 19]; 23(14):7991. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9318064/
2. Caron B, Honap S, Peyrin-Biroulet L. Epidemiology of inflammatory bowel disease across the ages in the era of advanced therapies. Journal of Crohns and Colitis [Internet]. 2024 [cited 2025 Oct 5];18(Supplement_2): ii3-15. Available from: https://dx.doi.org/10.1093/ecco-jcc/jjae082
3. Richard N, Savoye G, Leboutte M, Amamou A, Ghosh S, Marion-Letellier R. Crohn’s disease: Why the ileum? World Journal of Gastroenterology [Internet]. 2023 [cited 2025 Oct 5];29(21):3222-3240. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC10292140/
4. Elamir A, Shaker O, Kamal M, Khalefa A, Abdelwahed M, Reheem FA El, et al. Expression profile of serum LncRNA THRIL and MiR-125b in inflammatory bowel disease. PLoS One [Internet]. 2022 [cited 2025 Sep 13];17(10): e0275267. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9543963/
5. Zhang J, Guo Z, Wang Z, Zhu W, Li Q. Fecal miR‐223 is a noninvasive biomarker for estimating Crohn’s disease activity. Immunity Inflammation and Disease [Internet]. 2023 [cited 2025 Sep 13];11(12): e1131. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC10753866/
6. Elzoghby DMA, Mahmoud NH, Allam AS, Abdallah AM, Abdelghani AM. Serum miRNA 146b-5p a pharmacodynamic biomarker in adult inflammatory bowel disease. The Egyptian Journal of Immunology [Internet]. 2025 [cited 2025 Sep 13];32(3):40-47. Available from: https://doi.org/10.55133/eji.320305
7. Malham M, James JP, Jakobsen C, Hoegdall E, Holmstroem K, Wewer V, et al. Mucosal microRNAs relate to age and severity of disease in ulcerative colitis. Aging (Albany NY) [Internet]. 2021 [cited 2025 Sep 13];13(5):6359. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC7993741/
8. Voshagh Q, Anoshiravani A, Karimpour A, Goodarzi G, Tehrani SS, Tabatabaei-Malazy O, et al. Investigating the association between the tissue expression of miRNA-101, JAK2/STAT3 with TNF-α, IL-6, IL-1β, and IL-10 cytokines in the ulcerative colitis patients. Immunity, inflammation and Disease [Internet]. 2024 [cited 2025 Sep 13];12(3). Available from: https://pubmed.ncbi.nlm.nih.gov/38517042/
9. Zhou R, Qiu P, Wang H, Yang H, Yang X, Ye M, et al. Identification of microRNA-16-5p and microRNA-21-5p in feces as potential noninvasive biomarkers for inflammatory bowel disease. Aging (Albany NY) [Internet]. 2021 [cited 2025 Sep 13];13(3):4634. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC7906140/
10. Deissova T, Al Tukmachi D, Radova L, Bohosova J, Machackova T, Kren L, et al. Tissue MicroRNA expression signatures as diagnostic biomarkers and predictors of residual disease activity and relapses in treatment-naïve pediatric inflammatory bowel disease. Inflammatory Bowel Diseases [Internet]. 2025 [cited 2025 Sep 13];31(11):3033-3043. Available from: https://dx.doi.org/10.1093/ibd/izaf120
11. Luo S, Chen XH. Tissue and serum miR‐149‐3p/5p in hospitalized patients with inflammatory bowel disease: correlation with disease severity and inflammatory markers. The Kaohsiung Journal of Medical Sciences [Internet]. 2023 [cited 2025 Sep 13];40(2):13-138. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC11895588/
12. McDowell C, Farooq U, Haseeb M. Inflammatory bowel disease. StatPearls [Internet]. 2023 [cited 2025 Oct 12]; Available from: https://www.ncbi.nlm.nih.gov/books/NBK470312/
13. Rogler G, Singh A, Kavanaugh A, Rubin DT. Extraintestinal manifestations of inflammatory bowel disease: current concepts, treatment, and implications for disease management. Gastroenterology [Internet]. 2021 [cited 2025 Oct 19];161(4):1118-1132. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC8564770/
14. Whitney D Lynch, Ronald Hsu. Ulcerative colitis. StatPearls [Internet] 2023 [cited 2025 Oct 12]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459282/
15. Porter RJ, Kalla R, Ho GT. Ulcerative colitis: recent advances in the understanding of disease pathogenesis. F1000Research [Internet]. 2020 [cited 2025 Oct 19]; 9: F1000 Faculty Rev-294. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC7194476/
16. Beltrán B, Sáez-González E, Mateos B, Moret I. Enfermedad inflamatoria del tracto intestinal. Colitis ulcerosa. Medicine - Programa de Formación Médica Continuada Acreditado [Internet]. 2020 [citado 2025 Nov 16];13(11):591–602. Disponible en: https://www.sciencedirect.com/science/article/abs/pii/S0304541220301426
17. Indika R Ranasinghe, Chenlu Tian, Ronald Hsu. Crohn disease. StatPearls [Internet] 2024 [cited 2025 Oct 12]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK436021/
18. Wohnhaas CT, Schmid R, Rolser M, Kaaru E, Langgartner D, Rieber K, et al. Fecal MicroRNAs show promise as noninvasive crohn’s disease biomarkers. Crohn's & colitis 360 [Internet]. 2020 [cited 2025 Sep 13];2(1): otaa003. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC7291945/
19. Petagna L, Antonelli A, Ganini C, Bellato V, Campanelli M, Divizia A, et al. Pathophysiology of Crohn’s disease inflammation and recurrence. Biology Direct [Internet]. 2020 [cited 2025 Oct 19];15(1):23. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC7648997/
20. Ramadan YN, Kamel AM, Medhat MA, Hetta HF. MicroRNA signatures in the pathogenesis and therapy of inflammatory bowel disease. Clinical and Experimental Medicine [Internet]. 2024 [cited 2025 Sep 13];24(1):217. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC11390904/
21. Yarani R, Shojaeian A, Palasca O, Doncheva NT, Jensen LJ, Gorodkin J, et al. Differentially expressed miRNAs in ulcerative colitis and Crohn’s disease. Frontiers in Immunology [Internet]. 2022 [cited 2025 Jul 5]; 13:865777. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9208551/
22. Hu W, Fang T, Chen X. Identification of differentially expressed genes and miRNAs for ulcerative colitis using bioinformatics analysis. Frontiers in Genetics [Internet]. 2022 [cited 2025 Sep 13]; 13:914384. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9201719/
23. Onisor D, Brusnic O, Banescu C, Carstea C, Sasaran M, Stoian M, et al. miR-155 and miR-21 as Diagnostic and therapeutic biomarkers for ulcerative colitis: there is still a long way to go. Biomedicines [Internet]. 2024 [cited 2025 Sep 13]; 12(6):1315. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC11201222/
24. Saccon TD, Dhahbi JM, Schneider A, Nunez Lopez YO, Qasem A, Cavalcante MB, et al. Plasma miRNA Profile of Crohn’s disease and rheumatoid arthritis patients. Biology [Internet]. 2022 [cited 2025 Sep 13];11(4):508. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9033111/
25. Soroosh A, Fang K, Hoffman JM, Law IKM, Videlock E, Lokhandwala ZA, et al. Loss of miR-24-3p promotes epithelial cell apoptosis and impairs the recovery from intestinal inflammation. Cell Death & Disease [Internet]. 2021 [cited 2025 Oct 19]; 13(1):8. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC8684555/
26. de Oliveira ECS, Quaglio AEV, Grillo TG, Di Stasi LC, Sassaki LY. MicroRNAs in inflammatory bowel disease: What do we know and what can we expect? World Journal of Gastroenterology [Internet]. 2024 [cited 2025 Oct 18];30(16):2184-2190. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC11056918/
27. Atanassova A, Georgieva U. Circulating miRNA-16 in inflammatory bowel disease and some clinical correlations – a cohort study in Bulgarian patients. European Review for Medical Pharmacological Sciences [Internet]. 2022 [cited 2025 Sep 13]; 26 (17): 6310-6315. Available from: https://www.europeanreview.org/article/29655
28. Alfaifi J, Germain A, Heba AC, Arnone D, Gailly L, Ndiaye NC, et al. Deep Dive into MicroRNAs in inflammatory bowel disease. Inflammatory Bowel Diseases [Internet]. 2023 [cited 2025 Nov 24]; 29(6):986–99. Available from: https://academic.oup.com/ibdjournal/article/29/6/986/6955639
29. Yan H, Zhang X, Xu Y. Aberrant expression of miR-21 in patients with inflammatory bowel disease: a protocol for systematic review and meta-analysis. Medicine [Internet]. 2020 [cited 2025 Oct 25];99(17): e19693. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC7220677/
30. Li F, Yao JH, Li L, Nie Q, Cao JJ, Ning XR. MiRNA-23a-5p is the biomarkers for gouty arthritis and promotes inflammation in rats of gouty arthritis via MyD88/NF-κB pathway by induction TLR2. Archives of Rheumatology [Internet]. 2022 [cited 2025 Oct 18];37(4):536-546. Available from: https://pubmed.ncbi.nlm.nih.gov/36879567/
31. Soroosh A, Rankin CR, Polytarchou C, Lokhandwala ZA, Patel A, Chang L, et al. miR-24 Is elevated in ulcerative colitis patients and regulates intestinal epithelial barrier function. The American Journal of Pathology [Internet]. 2019 [cited 2025 Nov 9]; 189(9):1763–74. Available from: https://www.sciencedirect.com/science/article/pii/S0002944019300896
32. Mestrovic A, Perkovic N, Bozic D, Kumric M, Vilovic M, Bozic J. Precision medicine in inflammatory bowel disease: a spotlight on emerging molecular biomarkers. Biomedicines [Internet]. 2024 [cited 2025 Sep 13];12(7):1520. Available from: https://pubmed.ncbi.nlm.nih.gov/39062093/
33. Masi L, Capobianco I, Magrì C, Marafini I, Petito V, Scaldaferri F. MicroRNAs as innovative biomarkers for inflammatory bowel disease and prediction of colorectal cancer. International Journal of Molecular Sciences [Internet]. 2022 [cited 2025 Oct 19]; 23(14):7991. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9318064/