{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T21:25:25Z","timestamp":1791408325894,"version":"4.3.3"},"reference-count":78,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T00:00:00Z","timestamp":1651104000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre in Poland","doi-asserted-by":"publisher","award":["2020\/39\/O\/NZ4\/01732"],"award-info":[{"award-number":["2020\/39\/O\/NZ4\/01732"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Deficient mismatch repair (MMR) proteins may lead to DNA damage and microsatellite instability. Primary sclerosing cholangitis (PSC) is a risk factor for colitis-associated colon cancer. MiR-155 is suggested to act as a key regulating node, linking inflammation and tumorigenesis. However, its involvement in the chronic colitis of PSC-UC patients has not been examined. We investigated the involvement of miR-155 in the dysregulation of MMR genes and colitis in PSC patients. Colon tissue biopsies were obtained from patients with PSC, PSC with concomitant ulcerative colitis (PSC-UC), uncomplicated UC, and healthy controls (n = 10 per group). In the ascending colon of PSC and PSC-UC patients, upregulated miR-155 promoted high microsatellite instability and induced signal transducer and activator of transcription 3 (STAT-3) expression via the inhibition of suppressors of cytokine signalling 1 (SOCS1). In contrast, the absence of miR-155 overexpression in the sigmoid colon of PSC-UC patients activated the Il-6\/S1PR1 signalling pathway and imbalanced the IL17\/FOXP3 ratio, which reinforces chronic colitis. Functional studies on human intestinal epithelial cells (HT-29 and NCM460D) confirmed the role of miR-155 over-expression in the inhibition of MMR genes and the modulation of p53. Moreover, those cells produced more TNF\u03b1 upon a lipopolysaccharide challenge, which led to the suppression of miR-155. Additionally, exposure to bile acids induced upregulation of miR-155 in Caco-2 cell lines. Thus, under different conditions, miR-155 is involved in either neoplastic transformation in the ascending colon or chronic colitis in the sigmoid colon of patients with PSC. New insight into local modulation of microRNAs, that may alter the course of the disease, could be used for further research on potential therapeutic applications.<\/jats:p>","DOI":"10.3390\/ijms23094905","type":"journal-article","created":{"date-parts":[[2022,4,28]],"date-time":"2022-04-28T12:06:01Z","timestamp":1651147561000},"page":"4905","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Modulation of Mismatch Repair and the SOCS1\/p53 Axis by microRNA-155 in the Colon of Patients with Primary Sclerosing Cholangitis"],"prefix":"10.3390","volume":"23","author":[{"given":"Monika","family":"Adamowicz","sequence":"first","affiliation":[{"name":"Department of Medical Biology, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iga","family":"Stukan","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Milkiewicz","sequence":"additional","affiliation":[{"name":"Liver and Internal Medicine Unit, Medical University of Warsaw, 02-097 Warsaw, Poland"},{"name":"Translational Medicine Group, Pomeranian Medical University, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"Bialek","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malgorzata","family":"Milkiewicz","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7513-8640","authenticated-orcid":false,"given":"Agnieszka","family":"Kempinska-Podhorodecka","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1587","DOI":"10.1016\/S0140-6736(13)60096-3","article-title":"Primary sclerosing cholangitis","volume":"382","author":"Hirschfield","year":"2013","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1111\/j.1365-2036.2011.04753.x","article-title":"Review article: Colorectal neoplasia in patients with primary sclerosing cholangitis and inflammatory bowel disease","volume":"34","author":"Torres","year":"2011","journal-title":"Aliment. 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