miRNA-26b Overexpression in Ulcerative Colitis-associated Carcinogenesis

Benderska N, Dittrich AL, Knaup S, Rau T, Neufert C, Wach S, Fahlbusch FB, Rauh M, Wirtz RM, Agaimy A, Srinivasan S, Mahadevan V, Ruemmele P, Rapti E, Gazouli M, Hartmann A, Schneider-Stock R (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Book Volume: 21

Pages Range: 2039-51

Journal Issue: 9

DOI: 10.1097/MIB.0000000000000453

Abstract

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.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.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.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.

Authors with CRIS profile

Involved external institutions

STRATIFYER Molecular Pathology GmbH Germany (DE) Shanmugha Arts, Science, Technology & Research Academy (SASTRA University) India (IN) Universität Regensburg Germany (DE) National and Kapodistrian University of Athens Greece (GR)

How to cite

APA:

Benderska, N., Dittrich, A.-L., Knaup, S., Rau, T., Neufert, C., Wach, S.,... Schneider-Stock, R. (2015). miRNA-26b Overexpression in Ulcerative Colitis-associated Carcinogenesis. Inflammatory Bowel Diseases, 21(9), 2039-51. https://doi.org/10.1097/MIB.0000000000000453

MLA:

Benderska, Natalya, et al. "miRNA-26b Overexpression in Ulcerative Colitis-associated Carcinogenesis." Inflammatory Bowel Diseases 21.9 (2015): 2039-51.

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