Lewis, Amy and Felice, Carla and Kumagai, Tomoko and Lai, Cecilia and Singh, Kriti and Jeffery, Rosemary R and Feakins, Roger and Giannoulatou, Eleni and Armuzzi, Alessandro and Jawad, Noor and Lindsay, James O and Silver, Andrew (2017) The miR-200 family is increased in dysplastic lesions in ulcerative colitis patients. PloS One, 12 (3). pp. e0173664. ISSN 1932-6203 (Gold OA)
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Abstract
BACKGROUND
Colorectal cancer (CRC) is a life-threatening complication of ulcerative colitis (UC), and patients are routinely screened for the development of precancerous lesions (dysplasia). However, rates of CRC development in patients with confirmed low-grade dysplasia vary widely between studies, suggesting a large degree of heterogeneity between these lesions that is not detectable macroscopically. A better understanding of the underlying molecular changes that occur in dysplasia will help to identify lesions at higher risk of malignancy. MicroRNAs (miRNAs) post-transcriptionally regulate protein expression and cell-signalling networks. Aberrant miRNA expression is a feature of sporadic CRC but much less is known about the changes that occur in dysplasia and in UC.
METHODS
Comprehensive microRNA profiling was performed on RNA extracted from UC dysplastic lesions (n = 7) and UC controls (n = 10). The expression of miRNAs in UC post inflammatory polyps (n = 7) was also assessed. Candidate miRNAs were further validated by qPCR, and miRNA in situ hybridization. Serum levels of miRNAs were also assessed with a view to identification of non-invasive biomarkers of dysplasia.
RESULTS
UC dysplasia was associated with a shift in miRNA expression profiles that was not seen in inflammatory polyps. In particular, levels of miR-200b-3p were increased in dysplasia, and this miRNA was localised to epithelial cells in dysplastic lesions and in UC cancers. No changes in miRNA levels were detected in the serum.
CONCLUSION
UC-Dysplasia is linked to altered miRNA expression in the mucosa and elevated miR-200b-3p levels.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 16 Mar 2017 22:03 |
| Last Modified: | 17 Jan 2018 22:00 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/567 |
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