Benderska, Natalya and Dittrich, Anna-Lena and Knaup, Sabine and Rau, Tilman T. and Neufert, Clemens and Wach, Sven and Fahlbusch, Fabian B. and Rauh, Manfred and Wirtz, Ralph M. and Agaimy, Abbas and Srinivasan, Swetha and Mahadevan, Vijayalakshmi and Ruemmele, Petra and Rapti, Emmanouela and Gazouli, Maria and Hartmann, Arndt and Schneider-Stock, Regine (2015) miRNA-26b Overexpression in Ulcerative Colitis-associated Carcinogenesis. INFLAMMATORY BOWEL DISEASES, 21 (9). pp. 2039-2051. ISSN 1078-0998, 1536-4844
Full text not available from this repository. (Request a copy)Abstract
Background: Longstanding ulcerative colitis (UC) bears a high risk for development of UC-associated colorectal carcinoma (UCC). The inflammatory microenvironment influences microRNA expression, which in turn deregulates target gene expression. microRNA-26b (miR-26b) was shown to be instrumental in normal tissue growth and differentiation. Thus, we aimed to investigate the impact of miR-26b in inflammation-associated colorectal carcinogenesis. Methods: Two different cohorts of patients were investigated. In the retrospective group, a tissue microarray with 38 samples from 17 UC/UCC patients was used for miR-26b in situ hybridization and quantitative reverse transcription polymerase chain reaction analyses. In the prospective group, we investigated miR-26b expression in 25 fresh-frozen colon biopsies and corresponding serum samples of 6 UC and 15 non-UC patients, respectively. In silico analysis, Ago2-RNA immunoprecipitation, luciferase reporter assay, quantitative reverse transcription polymerase chain reaction examination, and miR-26b mimic overexpression were employed for target validation. Results: miR-26b expression was shown to be upregulated with disease progression in tissues and serum of UC and UCC patients. Using miR-26b and Ki-67 expression levels, an UCC was predicted with high accuracy. We identified 4 novel miR-26b targets (DIP1, MDM2, CREBBP, BRCA1). Among them, the downregulation of the E3 ubiquitin ligase DIP1 was closely related to death-associated protein kinase stabilization along the normal mucosa-UC-UCC sequence. In silico functional pathway analysis revealed that the common cellular pathways affected by miR-26b are highly related to cancerogenesis and the development of gastrointestinal diseases. Conclusions: We suggest that miR-26b could serve as a biomarker for inflammation-associated processes in the gastrointestinal system. Because miR-26b expression is downregulated in sporadic colon cancer, it could discriminate between UCC and the sporadic cancer type.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INFLAMMATORY-BOWEL-DISEASE; UBIQUITIN LIGASE; PROTEIN-KINASE; ANIMAL DEVELOPMENT; MIND BOMB; HEPATOCELLULAR-CARCINOMA; INDUCED APOPTOSIS; CELIAC-DISEASE; BREAST-CANCER; COLON-CANCER; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Jun 2019 13:42 |
| Last Modified: | 12 Jun 2019 13:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/4931 |
Actions (login required)
 |
View Item |
