{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T15:57:08Z","timestamp":1791561428660,"version":"4.3.4"},"reference-count":123,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T00:00:00Z","timestamp":1742256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>MicroRNAs (miRNAs) have emerged as crucial regulators in digestive pathologies, including inflammatory bowel disease (miR-31, miR-155, and miR-21), colorectal cancer (miR-21, miR-598, and miR-494), and non-alcoholic fatty liver disease (miR-21, miR-192, and miR-122). Their capacity to modulate gene expression at the post-transcriptional level makes them highly promising candidates for biomarkers and therapeutic interventions. However, despite considerable progress, their clinical application remains challenging. Research has shown that miRNA expression is highly dynamic, varying across patients, disease stages, and different intestinal regions. Their dual function as both oncogenes and tumor suppressors further complicates their therapeutic use, as targeting miRNAs may yield unpredictable effects. Additionally, while miRNA-based therapies hold great potential, significant hurdles persist, including off-target effects, immune activation, and inefficiencies in delivery methods. The intricate interplay between miRNAs and gut microbiota adds another layer of complexity, influencing disease mechanisms and treatment responses. This review examined the role of miRNAs in digestive pathologies, emphasizing their diagnostic and therapeutic potential. While they offer new avenues for disease management, unresolved challenges underscore the need for further research to refine their clinical application.<\/jats:p>","DOI":"10.3390\/jcm14062054","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T04:34:43Z","timestamp":1742272483000},"page":"2054","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["MicroRNAs in the Diagnosis of Digestive Diseases: A Comprehensive Review"],"prefix":"10.3390","volume":"14","author":[{"given":"Mirela Livia","family":"Popa","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9111-6088","authenticated-orcid":false,"given":"Cristian","family":"Ichim","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Anderco","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel Bogdan","family":"Todor","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Pop-Lodromanean","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Lucian Blaga University of Sibiu, 550169 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1146\/annurev.genom.8.080706.092351","article-title":"microRNAs in Vertebrate Physiology and Human Disease","volume":"8","author":"Chang","year":"2007","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s41544-019-0039-4","article-title":"Biogenesis and function of extracellular miRNAs","volume":"1","author":"Zhao","year":"2019","journal-title":"ExRNA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/S0092-8674(04)00045-5","article-title":"MicroRNAs: Genomics, biogenesis, mechanism, and function","volume":"116","author":"Bartel","year":"2004","journal-title":"Cell"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/nrg3965","article-title":"Towards a molecular understanding of microRNA-mediated gene silencing","volume":"16","author":"Jonas","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1177\/0300985813502820","article-title":"MicroRNAs: History, Biogenesis, and Their Evolving Role in Animal Development and Disease","volume":"51","author":"Bhaskaran","year":"2014","journal-title":"Vet. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1002\/bies.201200055","article-title":"Do miRNAs have a deep evolutionary history?","volume":"34","author":"Tarver","year":"2012","journal-title":"BioEssays"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1038\/cr.2008.282","article-title":"Characterization of microRNAs in serum: A novel class of biomarkers for diagnosis of cancer and other diseases","volume":"18","author":"Chen","year":"2008","journal-title":"Cell Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"10513","DOI":"10.1073\/pnas.0804549105","article-title":"Circulating microRNAs as stable blood-based markers for cancer detection","volume":"105","author":"Mitchell","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1111\/j.1349-7006.2010.01650.x","article-title":"Circulating microRNA in body fluid: A new potential biomarker for cancer diagnosis and prognosis","volume":"101","author":"Kosaka","year":"2010","journal-title":"Cancer Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1016\/j.cell.2010.11.012","article-title":"Ubiquitin: Same Molecule, Different Degradation Pathways","volume":"143","author":"Clague","year":"2010","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e1297","DOI":"10.1097\/MD.0000000000001297","article-title":"MicroRNA Expression Profile Reveals miR-17-92 and miR-143-145 Cluster in Synchronous Colorectal Cancer","volume":"94","author":"Meng","year":"2015","journal-title":"Medicine"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"James, J.P., Riis, L.B., Malham, M., H\u00f8gdall, E., Langholz, E., and Nielsen, B.S. (2020). MicroRNA Biomarkers in IBD\u2014Differential Diagnosis and Prediction of Colitis-Associated Cancer. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21217893"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1093\/ibd\/izy046","article-title":"Circulating and Fecal microRNAs as Biomarkers for Inflammatory Bowel Diseases","volume":"24","author":"Le","year":"2018","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Masi, L., Capobianco, I., Magr\u00ec, C., Marafini, I., Petito, V., and Scaldaferri, F. (2022). MicroRNAs as Innovative Biomarkers for Inflammatory Bowel Disease and Prediction of Colorectal Cancer. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23147991"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.3390\/jcm4121953","article-title":"MicroRNAs in Nonalcoholic Fatty Liver Disease","volume":"4","author":"Baffy","year":"2015","journal-title":"J. Clin. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S193","DOI":"10.33549\/physiolres.935153","article-title":"Circulating exosomal miRNAs as a promising diagnostic biomarker in cancer","volume":"72","author":"Bugala","year":"2023","journal-title":"Physiol. Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Patil, N., Abdelrahim, O.G., Leupold, J.H., and Allgayer, H. (2023). JAK1 Is a Novel Target of Tumor- and Invasion-Suppressive microRNA 494-5p in Colorectal Cancer. Cancers, 16.","DOI":"10.3390\/cancers16010024"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"M\u00f8ller, T., James, J.P., Holmstr\u00f8m, K., S\u00f8rensen, F.B., Lindebjerg, J., and Nielsen, B.S. (2019). Co-Detection of miR-21 and TNF-\u03b1 mRNA in Budding Cancer Cells in Colorectal Cancer. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20081907"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/0092-8674(93)90529-Y","article-title":"The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14","volume":"75","author":"Lee","year":"1993","journal-title":"Cell"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1016\/S0960-9822(03)00287-2","article-title":"MicroRNAs and Other Tiny Endogenous RNAs in C. elegans","volume":"13","author":"Ambros","year":"2003","journal-title":"Curr. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1136\/gutjnl-2014-307891","article-title":"MicroRNAs: New players in IBD","volume":"64","author":"Kalla","year":"2015","journal-title":"Gut"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1053\/j.gastro.2010.07.040","article-title":"MicroRNAs Control Intestinal Epithelial Differentiation, Architecture, and Barrier Function","volume":"139","author":"McKenna","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.3390\/cancers7030842","article-title":"MicroRNAs in Cancer: A Historical Perspective on the Path from Discovery to Therapy","volume":"7","author":"Orellana","year":"2015","journal-title":"Cancers"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1053\/j.gastro.2011.07.005","article-title":"MicroRNA Regulation of Intestinal Epithelial Tight Junction Permeability","volume":"141","author":"Ye","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1053\/j.gastro.2014.09.037","article-title":"MicroRNA 29 Targets Nuclear Factor-\u03baB\u2013Repressing Factor and Claudin 1 to Increase Intestinal Permeability","volume":"148","author":"Zhou","year":"2015","journal-title":"Gastroenterology"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Fasseu, M., Tr\u00e9ton, X., Guichard, C., Pedruzzi, E., Cazals-Hatem, D., Richard, C., Aparicio, T., Daniel, F., Soul\u00e9, J.-C., and Moreau, R. (2010). Identification of Restricted Subsets of Mature microRNA Abnormally Expressed in Inactive Colonic Mucosa of Patients with Inflammatory Bowel Disease. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013160"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1007\/s12035-023-03600-8","article-title":"MiR-26b-3p Promotes Intestinal Motility Disorder by Targeting FZD10 to Inhibit GSK3\u03b2\/\u03b2-Catenin Signaling and Induce Enteric Glial Cell Apoptosis","volume":"61","author":"Zhan","year":"2024","journal-title":"Mol. Neurobiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1007\/s12664-020-01143-7","article-title":"miR-222 regulates cell growth, apoptosis, and autophagy of interstitial cells of Cajal isolated from slow transit constipation rats by targeting c-kit","volume":"40","author":"Zheng","year":"2021","journal-title":"Indian J. Gastroenterol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1261\/rna.1699809","article-title":"Quantitative miRNA expression analysis: Comparing microarrays with next-generation sequencing","volume":"15","author":"Willenbrock","year":"2009","journal-title":"RNA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1038\/nmeth0709-474","article-title":"Limitations and possibilities of small RNA digital gene expression profiling","volume":"6","author":"Linsen","year":"2009","journal-title":"Nat. Methods"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1261\/rna.1947110","article-title":"Systematic comparison of microarray profiling, real-time PCR, and next-generation sequencing technologies for measuring differential microRNA expression","volume":"16","author":"Git","year":"2010","journal-title":"RNA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1093\/abbs\/gmq114","article-title":"Stability analysis of liver cancer-related microRNAs","volume":"43","author":"Li","year":"2011","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Wagatsuma, K., Yokoyama, Y., and Nakase, H. (2021). Role of Biomarkers in the Diagnosis and Treatment of Inflammatory Bowel Disease. Life, 11.","DOI":"10.3390\/life11121375"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1007\/s00384-024-04711-x","article-title":"Global, regional, and national burden of inflammatory bowel disease, 1990-2021: Insights from the global burden of disease 2021","volume":"39","author":"Lin","year":"2024","journal-title":"Int. J. Color. Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S2468-1253(19)30333-4","article-title":"The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990\u20132017: A systematic analysis for the Global Burden of Disease Study 2017","volume":"5","author":"Alatab","year":"2020","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_36","unstructured":"Mokhtari, R., Hamidinekoo, A., Sutton, D., Lewis, A., Angermann, B., Gehrmann, U., Lundin, P., Adissu, H., Cairns, J., and Neisen, J. (2023). Interpretable histopathology-based prediction of disease relevant features in Inflammatory Bowel Disease biopsies using weakly-supervised deep learning. arXiv."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1053\/j.gastro.2007.09.001","article-title":"Diagnostics of Inflammatory Bowel Disease","volume":"133","author":"Nikolaus","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1093\/ecco-jcc\/jjy113","article-title":"ECCO-ESGAR Guideline for Diagnostic Assessment in IBD Part 1: Initial diagnosis, monitoring of known IBD, detection of complications","volume":"13","author":"Maaser","year":"2019","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/ibd.21359","article-title":"Dynamic changes in the expression of MicroRNA-31 during inflammatory bowel disease-associated neoplastic transformation","volume":"17","author":"Olaru","year":"2011","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1053\/j.gastro.2008.07.068","article-title":"MicroRNAs Are Differentially Expressed in Ulcerative Colitis and Alter Expression of Macrophage Inflammatory Peptide-2\u03b1","volume":"135","author":"Wu","year":"2008","journal-title":"Gastroenterology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/s00428-012-1345-5","article-title":"PDCD4\/miR-21 dysregulation in inflammatory bowel disease-associated carcinogenesis","volume":"462","author":"Ludwig","year":"2013","journal-title":"Virchows Arch."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.autrev.2010.07.002","article-title":"MicroRNAs in autoimmunity and inflammatory bowel disease: Crucial regulators in immune response","volume":"11","author":"Iborra","year":"2012","journal-title":"Autoimmun. Rev."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Peacock, O., Lee, A.C., Cameron, F., Tarbox, R., Vafadar-Isfahani, N., Tufarelli, C., and Lund, J.N. (2014). Inflammation and MiR-21 Pathways Functionally Interact to Downregulate PDCD4 in Colorectal Cancer. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0110267"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1111\/apt.15159","article-title":"Circulating microRNA146b-5p is superior to C-reactive protein as a novel biomarker for monitoring inflammatory bowel disease","volume":"49","author":"Chen","year":"2019","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Rashid, H., Hossain, B., Siddiqua, T., Kabir, M., Noor, Z., Ahmed, M., and Haque, R. (2020). Fecal MicroRNAs as Potential Biomarkers for Screening and Diagnosis of Intestinal Diseases. Front. Mol. Biosci., 7.","DOI":"10.3389\/fmolb.2020.00181"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Schaefer, J.S., Attumi, T., Opekun, A.R., Abraham, B., Hou, J., Shelby, H., Graham, D.Y., Streckfus, C., and Klein, J.R. (2015). MicroRNA signatures differentiate Crohn\u2019s disease from ulcerative colitis. BMC Immunol., 16.","DOI":"10.1186\/s12865-015-0069-0"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Ben-Shachar, S., Yanai, H., Sherman Horev, H., Elad, H., Baram, L., Issakov, O., Tulchinsky, H., Pasmanik-Chor, M., Shomron, N., and Dotan, I. (2016). MicroRNAs Expression in the Ileal Pouch of Patients with Ulcerative Colitis Is Robustly Up-Regulated and Correlates with Disease Phenotypes. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0159956"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Zhou, J., Liu, J., Gao, Y., Shen, L., Li, S., and Chen, S. (2021). miRNA-Based Potential Biomarkers and New Molecular Insights in Ulcerative Colitis. Front. Pharmacol., 12.","DOI":"10.3389\/fphar.2021.707776"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"otaa003","DOI":"10.1093\/crocol\/otaa003","article-title":"Fecal MicroRNAs Show Promise as Noninvasive Crohn\u2019s Disease Biomarkers","volume":"2","author":"Wohnhaas","year":"2020","journal-title":"Crohn\u2019s Colitis 360"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1097\/MPG.0b013e31822200cc","article-title":"Circulating microRNA is a biomarker of pediatric Crohn disease","volume":"53","author":"Zahm","year":"2011","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Boccatonda, A., Andreetto, L., D\u2019Ardes, D., Cocco, G., Rossi, I., Vicari, S., Schiavone, C., Cipollone, F., and Guagnano, M.T. (2023). From NAFLD to MAFLD: Definition, Pathophysiological Basis and Cardiovascular Implications. Biomedicines, 11.","DOI":"10.3390\/biomedicines11030883"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1017\/S0954422421000056","article-title":"Effects of betaine on non-alcoholic liver disease","volume":"35","author":"Chen","year":"2022","journal-title":"Nutr. Res. Rev."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"154809","DOI":"10.1016\/j.prp.2023.154809","article-title":"A crosstalk between epigenetic modulations and non-alcoholic fatty liver disease progression","volume":"251","author":"Ramezani","year":"2023","journal-title":"Pathol. Res. Pract."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease\u2014Meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.4254\/wjh.v7.i24.2497","article-title":"Epigenetic mechanisms in non-alcoholic fatty liver disease: An emerging field","volume":"7","year":"2015","journal-title":"World J. Hepatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.jhep.2018.10.033","article-title":"Non-Alcoholic fatty liver disease\u2014A global public health perspective","volume":"70","author":"Younossi","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1093\/cvr\/cvad095","article-title":"Non-alcoholic fatty liver disease: Pathophysiological concepts and treatment options","volume":"119","author":"Grander","year":"2023","journal-title":"Cardiovasc. Res."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Shi, Y., and Qi, W. (2023). Histone Modifications in NAFLD: Mechanisms and Potential Therapy. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241914653"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Dongiovanni, P., Meroni, M., Longo, M., Fargion, S., and Fracanzani, A.L. (2018). miRNA Signature in NAFLD: A Turning Point for a Non-Invasive Diagnosis. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19123966"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1016\/j.jhep.2018.08.008","article-title":"miRNAs in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis","volume":"69","author":"Liu","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Del Campo, J., Gallego-Dur\u00e1n, R., Gallego, P., and Grande, L. (2018). Genetic and Epigenetic Regulation in Nonalcoholic Fatty Liver Disease (NAFLD). Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19030911"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1136\/gutjnl-2014-306996","article-title":"Circulating microRNA signature in non-alcoholic fatty liver disease: From serum non-coding RNAs to liver histology and disease pathogenesis","volume":"64","author":"Pirola","year":"2015","journal-title":"Gut"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1186\/s12967-024-05554-4","article-title":"A systematic review of non-coding RNA therapeutics in early clinical trials: A new perspective against cancer","volume":"22","author":"Grillone","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1715","DOI":"10.1007\/s12072-024-10722-1","article-title":"Dynamic role of exosomal long non-coding RNA in liver diseases: Pathogenesis and diagnostic aspects","volume":"18","author":"Ismail","year":"2024","journal-title":"Hepatol. Int."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Liu, J., Xiao, Y., Wu, X., Jiang, L., Yang, S., Ding, Z., Fang, Z., Hua, H., Kirby, M.S., and Shou, J. (2018). A circulating microRNA signature as noninvasive diagnostic and prognostic biomarkers for nonalcoholic steatohepatitis. BMC Genom., 19.","DOI":"10.1186\/s12864-018-4575-3"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1053\/j.gastro.2012.04.007","article-title":"MicroRNAs in Liver Disease","volume":"142","author":"Wang","year":"2012","journal-title":"Gastroenterology"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Drescher, H., Weiskirchen, S., and Weiskirchen, R. (2019). Current Status in Testing for Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH). Cells, 8.","DOI":"10.3390\/cells8080845"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"83245","DOI":"10.1007\/s11356-023-28223-3","article-title":"Global, region and national trends and age-period-cohort effects in colorectal cancer burden from 1990 to 2019, with predictions to 2039","volume":"30","author":"Hu","year":"2023","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s10654-023-01073-6","article-title":"Impact of organised colorectal cancer screening on age-specific population incidences: Evidence from a quasi-experimental study in Sweden","volume":"39","author":"Forsberg","year":"2024","journal-title":"Eur. J. Epidemiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"7882","DOI":"10.3748\/wjg.v22.i35.7882","article-title":"Biomarkers for colitis-associated colorectal cancer","volume":"22","author":"Chen","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1093\/ecco-jcc\/jjab102","article-title":"Inflammatory Bowel Disease-Associated Colorectal Cancer: Translational Risks from Mechanisms to Medicines","volume":"15","author":"Porter","year":"2021","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s10585-010-9355-7","article-title":"High levels of microRNA-21 in the stroma of colorectal cancers predict short disease-free survival in stage II colon cancer patients","volume":"28","author":"Nielsen","year":"2011","journal-title":"Clin. Exp. Metastasis"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.gene.2015.04.065","article-title":"Differential expressions of cancer-associated genes and their regulatory miRNAs in colorectal carcinoma","volume":"567","author":"Kara","year":"2015","journal-title":"Gene"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Zhou, L., Liu, H., Chen, Z., Chen, S., Lu, J., Liu, C., Liao, S., He, S., Chen, S., and Zhou, Z. (2023). Downregulation of miR-182-5p by NFIB promotes NAD+ salvage synthesis in colorectal cancer by targeting NAMPT. Commun. Biol., 6.","DOI":"10.1038\/s42003-023-05143-z"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Dai, W., Hong, L., Xiao, W., Zhang, L., Sha, W., Yu, Z., Liu, X., Liu, S., Xiao, Y., and Yang, P. (2023). The ATF2\/miR-3913-5p\/CREB5 axis is involved in the cell proliferation and metastasis of colorectal cancer. Commun. Biol., 6.","DOI":"10.1038\/s42003-023-05405-w"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"60149","DOI":"10.18632\/oncotarget.18557","article-title":"Exosome-Encapsulated microRNAs as circulating biomarkers for colorectal cancer","volume":"8","author":"Yan","year":"2017","journal-title":"Oncotarget"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"76250","DOI":"10.18632\/oncotarget.12841","article-title":"Serum exosomal miR-4772-3p is a predictor of tumor recurrence in stage II and III colon cancer","volume":"7","author":"Liu","year":"2016","journal-title":"Oncotarget"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1457","DOI":"10.1002\/jcb.27291","article-title":"Downregulation of exosome-encapsulated miR-548c-5p is associated with poor prognosis in colorectal cancer","volume":"120","author":"Peng","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"107206","DOI":"10.1016\/j.isci.2023.107206","article-title":"IDH1 K224 acetylation promotes colorectal cancer via miR-9-5p\/NHE1 axis-mediated regulation of acidic microenvironment","volume":"26","author":"Wang","year":"2023","journal-title":"iScience"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"109168","DOI":"10.1016\/j.isci.2024.109168","article-title":"CircTBC1D22A inhibits the progression of colorectal cancer through autophagy regulated via miR-1825\/ATG14 axis","volume":"27","author":"Sun","year":"2024","journal-title":"iScience"},{"key":"ref_81","first-page":"511","article-title":"The histopathological approach to inflammatory bowel disease: A practice guide","volume":"464","author":"Langner","year":"2014","journal-title":"Virchows Arch."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"2112","DOI":"10.7150\/ijbs.59904","article-title":"Roles of microRNAs in inflammatory bowel disease","volume":"17","author":"Jung","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1002\/ibd.21267","article-title":"Identification of microRNAs associated with ileal and colonic Crohn\u2019s disease","volume":"16","author":"Wu","year":"2010","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"S129","DOI":"10.1111\/j.1440-1746.2009.06216.x","article-title":"Increased expression of microRNA in the inflamed colonic mucosa of patients with active ulcerative colitis","volume":"25","author":"Takagi","year":"2010","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"4629","DOI":"10.3748\/wjg.v18.i34.4629","article-title":"MicroRNAs in inflammatory bowel disease\u2014Pathogenesis, diagnostics and therapeutics","volume":"18","author":"Coskun","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1189\/jlb.0604341","article-title":"BALB\/c mice have more CD4+CD25+ T regulatory cells and show greater susceptibility to suppression of their CD4+CD25\u2212 responder T cells than C57BL\/6 mice","volume":"78","author":"Chen","year":"2005","journal-title":"J. Leukoc. Biol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1016\/j.cmet.2023.04.013","article-title":"Extracellular vesicles in fatty liver promote a metastatic tumor microenvironment","volume":"35","author":"Wang","year":"2023","journal-title":"Cell Metab."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/s10020-019-0085-2","article-title":"miR-122 promotes hepatic lipogenesis via inhibiting the LKB1\/AMPK pathway by targeting Sirt1 in non-alcoholic fatty liver disease","volume":"25","author":"Long","year":"2019","journal-title":"Mol. Med."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/s11894-023-00883-8","article-title":"Screening, Diagnosis, and Staging of Non-Alcoholic Fatty Liver Disease (NAFLD): Application of Society Guidelines to Clinical Practice","volume":"25","author":"Banini","year":"2023","journal-title":"Curr. Gastroenterol. Rep."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Baranova, A., Lal, P., Birerdinc, A., and Younossi, Z.M. (2011). Non-Invasive markers for hepatic fibrosis. BMC Gastroenterol., 11.","DOI":"10.1186\/1471-230X-11-91"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Newman, L.A., Useckaite, Z., Johnson, J., Sorich, M.J., Hopkins, A.M., and Rowland, A. (2022). Selective Isolation of Liver-Derived Extracellular Vesicles Redefines Performance of miRNA Biomarkers for Non-Alcoholic Fatty Liver Disease. Biomedicines, 10.","DOI":"10.3390\/biomedicines10010195"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Afonso, M., Rodrigues, P., Sim\u00e3o, A., and Castro, R. (2016). Circulating microRNAs as Potential Biomarkers in Non-Alcoholic Fatty Liver Disease and Hepatocellular Carcinoma. J. Clin. Med., 5.","DOI":"10.3390\/jcm5030030"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.lfs.2018.07.029","article-title":"Plasma miR-17, miR-20a, miR-20b and miR-122 as potential biomarkers for diagnosis of NAFLD in type 2 diabetes mellitus patients","volume":"208","author":"Ye","year":"2018","journal-title":"Life Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1002\/hep.27153","article-title":"Inhibition of microRNA-24 expression in liver prevents hepatic lipid accumulation and hyperlipidemia: NG ET AL","volume":"60","author":"Ng","year":"2014","journal-title":"Hepatology"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"108352","DOI":"10.1016\/j.isci.2023.108352","article-title":"MiR-337-3p improves metabolic-associated fatty liver disease through regulation of glycolipid metabolism","volume":"26","author":"Xu","year":"2023","journal-title":"iScience"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"154375","DOI":"10.1016\/j.prp.2023.154375","article-title":"The role of miRNAs in liver diseases: Potential therapeutic and clinical applications","volume":"243","author":"Doghish","year":"2023","journal-title":"Pathol. Res. Pract."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Sakai, E., Imaizumi, T., Suzuki, R., Taracena-G\u00e1ndara, M., Fujimoto, T., Sakurai, F., and Mizuguchi, H. (2023). miR-27b targets MAIP1 to mediate lipid accumulation in cultured human and mouse hepatic cells. Commun. Biol., 6.","DOI":"10.1038\/s42003-023-05049-w"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.7150\/ijbs.59588","article-title":"MicroRNAs in the Pathogenesis of Nonalcoholic Fatty Liver Disease","volume":"17","author":"Fang","year":"2021","journal-title":"Int. J. Biol. Sci."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1136\/gutjnl-2018-318146","article-title":"miRNAs and NAFLD: From pathophysiology to therapy","volume":"68","author":"Gjorgjieva","year":"2019","journal-title":"Gut"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.canlet.2020.12.025","article-title":"Dissecting miRNA signature in colorectal cancer progression and metastasis","volume":"501","author":"Huang","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"9575","DOI":"10.1007\/s11033-023-08810-w","article-title":"MicroRNAs and colorectal cancer: Clinical potential and regulatory networks","volume":"50","author":"Osei","year":"2023","journal-title":"Mol. Biol. Rep."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"AlZaabi, A., and Shalaby, A. (2024). A Systematic Review of Diagnostic Performance of Circulating MicroRNAs in Colorectal Cancer Detection with a Focus on Early-Onset Colorectal Cancer. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25179565"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1968","DOI":"10.1038\/onc.2014.134","article-title":"MicroRNA-885-3p inhibits the growth of HT-29 colon cancer cell xenografts by disrupting angiogenesis via targeting BMPR1A and blocking BMP\/Smad\/Id1 signaling","volume":"34","author":"Xiao","year":"2015","journal-title":"Oncogene"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s12943-020-01174-w","article-title":"MIR22HG acts as a tumor suppressor via TGF\u03b2\/SMAD signaling and facilitates immunotherapy in colorectal cancer","volume":"19","author":"Xu","year":"2020","journal-title":"Mol. Cancer"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"21098","DOI":"10.1073\/pnas.1015541107","article-title":"MicroRNA-21 induces resistance to 5-fluorouracil by down-regulating human DNA MutS homolog 2 (hMSH2)","volume":"107","author":"Valeri","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Aggeletopoulou, I., Mouzaki, A., Thomopoulos, K., and Triantos, C. (2023). miRNA Molecules\u2014Late Breaking Treatment for Inflammatory Bowel Diseases?. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032233"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Bocchetti, M., Ferraro, M.G., Ricciardiello, F., Ottaiano, A., Luce, A., Cossu, A.M., Scrima, M., Leung, W.-Y., Abate, M., and Stiuso, P. (2021). The Role of microRNAs in Development of Colitis-Associated Colorectal Cancer. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22083967"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"2199","DOI":"10.1038\/cdd.2017.151","article-title":"miR-148a inhibits colitis and colitis-associated tumorigenesis in mice","volume":"24","author":"Zhu","year":"2017","journal-title":"Cell Death Differ."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Zhu, Y., Tan, J.K., Wong, S.K., and Goon, J.A. (2023). Therapeutic Effects of microRNAs on Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH): A Systematic Review and Meta-Analysis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119168"},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Wang, X., Zhang, D., Yang, Y., Li, X., Li, H., Zhang, X., Long, J., Lu, Y., Liu, L., and Yang, G. (2023). Suppression of microRNA-222-3p ameliorates ulcerative colitis and colitis-associated colorectal cancer to protect against oxidative stress via targeting BRG1 to activate Nrf2\/HO-1 signaling pathway. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1089809"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1093\/ecco-jcc\/jjaa204","article-title":"miR-130a-3p, a Preclinical Therapeutic Target for Crohn\u2019s Disease","volume":"15","author":"Zhao","year":"2021","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s41544-019-0026-9","article-title":"microRNAs as therapeutic targets in intestinal diseases","volume":"1","author":"Wang","year":"2019","journal-title":"ExRNA"},{"key":"ref_113","doi-asserted-by":"crossref","unstructured":"Momin, M.Y., Gaddam, R.R., Kravitz, M., Gupta, A., and Vikram, A. (2021). The Challenges and Opportunities in the Development of MicroRNA Therapeutics: A Multidisciplinary Viewpoint. Cells, 10.","DOI":"10.3390\/cells10113097"},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Dalmasso, G., Nguyen, H.T.T., Yan, Y., Laroui, H., Charania, M.A., Ayyadurai, S., Sitaraman, S.V., and Merlin, D. (2011). Microbiota Modulate Host Gene Expression via MicroRNAs. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0019293"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1093\/ecco-jcc\/jjab223","article-title":"MicroRNA and Gut Microbiota: Tiny but Mighty\u2014Novel Insights into Their Cross-talk in Inflammatory Bowel Disease Pathogenesis and Therapeutics","volume":"16","author":"Viennois","year":"2022","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1007\/s10620-022-07516-6","article-title":"Functional Implications and Clinical Potential of MicroRNAs in Irritable Bowel Syndrome: A Concise Review","volume":"68","author":"Pathak","year":"2023","journal-title":"Dig. Dis. Sci."},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Suri, K., Bubier, J.A., Wiles, M.V., Shultz, L.D., Amiji, M.M., and Hosur, V. (2021). Role of MicroRNA in Inflammatory Bowel Disease: Clinical Evidence and the Development of Preclinical Animal Models. Cells, 10.","DOI":"10.3390\/cells10092204"},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Komatsu, S., Kitai, H., and Suzuki, H.I. (2023). Network Regulation of microRNA Biogenesis and Target Interaction. Cells, 12.","DOI":"10.3390\/cells12020306"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Giammona, A., Galuzzi, B.G., Imperia, E., Gervasoni, C., Remedia, S., Restaneo, L., Nespoli, M., De Gara, L., Tani, F., and Cicala, M. (2025). Chronic Gastrointestinal Disorders and miRNA-Associated Disease: An Up-to-Date. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26010413"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1038\/nrd4359","article-title":"Therapeutic targeting of microRNAs: Current status and future challenges","volume":"13","author":"Li","year":"2014","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s41544-019-0024-y","article-title":"Recent progress in microRNA-based delivery systems for the treatment of human disease","volume":"1","author":"Fu","year":"2019","journal-title":"ExRNA"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Forterre, A., Komuro, H., Aminova, S., and Harada, M. (2020). A Comprehensive Review of Cancer MicroRNA Therapeutic Delivery Strategies. Cancers, 12.","DOI":"10.3390\/cancers12071852"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Yang, Y., Meng, W.-J., and Wang, Z.-Q. (2022). MicroRNAs (miRNAs): Novel potential therapeutic targets in colorectal cancer. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1054846"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/6\/2054\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:55:32Z","timestamp":1760028932000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/14\/6\/2054"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,18]]},"references-count":123,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["jcm14062054"],"URL":"https:\/\/doi.org\/10.3390\/jcm14062054","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,18]]}}}