Disease- and Region-Specific Molecular Patterns Involving miRNAs and Associated Signalling Pathways and Epithelial Cell-Fate Responses in PSC-Associated Ulcerative Colitis.
6 affiliations
- 1Department of Functional Anatomy, Pomeranian Medical University in Szczecin, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland.
- 2Department of Medical Biology, Pomeranian Medical University in Szczecin, Powstańców Wielkopolskich 72, 70-111 Szczecin, Poland.
- 3Department of Gastroenterology, Pomeranian Medical University in Szczecin, Unii Lubelskiej 1, 71-252 Szczecin, Poland.
- 4Department of Clinical Anatomy, Pomeranian Medical University in Szczecin, Ku Słońcu 12, 71-073 Szczecin, Poland.
- 5Liver and Internal Medicine Unit, Department of General, Transplant and Liver Surgery, Medical University of Warsaw, 02-091 Warsaw, Poland.
- 6Translational Medicine Group, Pomeranian Medical University in Szczecin, 70-204 Szczecin, Poland.
Abstract
Patients with primary sclerosing cholangitis-associated ulcerative colitis (PSC-UC) have an elevated risk of colorectal cancer compared with ulcerative colitis (UC), but the molecular mechanisms linking chronic inflammation to epithelial cell fate remain unclear. The present study investigated disease- and region-specific molecular patterns involving miRNAs and associated PI3K/AKT, STAT3, and NF-κB signalling pathways. miR-21, miR-181a, miR-181b, and key pathway components were analysed in paired ascending and sigmoid colon biopsies from patients with PSC, PSC-UC, UC, and controls. Functional effects were examined in HT-29 and NCM460D cells, and circulating miRNAs, including miR-155, were assessed. UC was characterised by marked miR-181a upregulation and PI3K/AKT activation, whereas PSC-UC showed reduced PDCD4, divergent p65 regulation, and altered miR-181a/miR-181b coordination. In NCM460D cells, miR-181a and miR-181b reduced viability, promoted apoptosis, impaired cell-cycle progression, and decreased PDCD4, p-AKT, and p-STAT3; miR-181b additionally reduced CYLD. Serum miR-155 was elevated in PSC-UC compared with UC and showed the strongest individual discriminatory capacity. Random forest analysis and an exploratory multivariable serum miRNA profile showed discriminatory potential. These findings support disease- and region-specific molecular patterns involving miRNAs and associated signalling pathways linked to epithelial cell-fate responses in PSC-UC and highlight molecular differences between PSC-UC and conventional UC.
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BibTeX
@article{laba2026disease,
title = {{Disease- and Region-Specific Molecular Patterns Involving miRNAs and Associated Signalling Pathways and Epithelial Cell-Fate Responses in PSC-Associated Ulcerative Colitis.}},
author = {Alicja Łaba and Joanna Abramczyk and Michał Lubkowski and Wiesława Rogoza-Mateja and Malgorzata Milkiewicz and Oktawian Knap and Piotr Milkiewicz and Agnieszka Kempinska-Podhorodecka},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15191821},
url = {https://europepmc.org/article/MED/42882519},
note = {CC BY},
}
RIS
TY - JOUR
TI - Disease- and Region-Specific Molecular Patterns Involving miRNAs and Associated Signalling Pathways and Epithelial Cell-Fate Responses in PSC-Associated Ulcerative Colitis.
AU - Alicja Łaba
AU - Joanna Abramczyk
AU - Michał Lubkowski
AU - Wiesława Rogoza-Mateja
AU - Malgorzata Milkiewicz
AU - Oktawian Knap
AU - Piotr Milkiewicz
AU - Agnieszka Kempinska-Podhorodecka
PY - 2026
DA - 2026/10/07
JO - Cells
DO - 10.3390/cells15191821
UR - https://europepmc.org/article/MED/42882519
AB - Patients with primary sclerosing cholangitis-associated ulcerative colitis (PSC-UC) have an elevated risk of colorectal cancer compared with ulcerative colitis (UC), but the molecular mechanisms linking chronic inflammation to epithelial cell fate remain unclear. The present study investigated disease- and region-specific molecular patterns involving miRNAs and associated PI3K/AKT, STAT3, and NF-κB signalling pathways. miR-21, miR-181a, miR-181b, and key pathway components were analysed in paired ascending and sigmoid colon biopsies from patients with PSC, PSC-UC, UC, and controls. Functional effects were examined in HT-29 and NCM460D cells, and circulating miRNAs, including miR-155, were assessed. UC was characterised by marked miR-181a upregulation and PI3K/AKT activation, whereas PSC-UC showed reduced PDCD4, divergent p65 regulation, and altered miR-181a/miR-181b coordination. In NCM460D cells, miR-181a and miR-181b reduced viability, promoted apoptosis, impaired cell-cycle progression, and decreased PDCD4, p-AKT, and p-STAT3; miR-181b additionally reduced CYLD. Serum miR-155 was elevated in PSC-UC compared with UC and showed the strongest individual discriminatory capacity. Random forest analysis and an exploratory multivariable serum miRNA profile showed discriminatory potential. These findings support disease- and region-specific molecular patterns involving miRNAs and associated signalling pathways linked to epithelial cell-fate responses in PSC-UC and highlight molecular differences between PSC-UC and conventional UC.
SN - 2073-4409
ER -