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- Title
Epigenetic silencing of the intronic microRNA hsa-miR-342 and its host gene EVL in colorectal cancer.
- Authors
Grady, W M; Parkin, R K; Mitchell, P S; Lee, J H; Kim, Y-H; Tsuchiya, K D; Washington, M K; Paraskeva, C; Willson, J K V; Kaz, A M; Kroh, E M; Allen, A; Fritz, B R; Markowitz, S D; Tewari, M
- Abstract
MicroRNAs are small, non-coding RNAs that influence gene regulatory networks by post-transcriptional regulation of specific messenger RNA targets. MicroRNA expression is dysregulated in human malignancies, frequently leading to loss of expression of certain microRNAs. We report that expression of hsa-miR-342, a microRNA encoded in an intron of the gene EVL, is commonly suppressed in human colorectal cancer. The expression of hsa-miR-342 is coordinated with that of EVL and our results indicate that the mechanism of silencing is CpG island methylation upstream of EVL. We found methylation at the EVL/hsa-miR-342 locus in 86% of colorectal adenocarcinomas and in 67% of adenomas, indicating that it is an early event in colorectal carcinogenesis. In addition, we observed a higher frequency of methylation (56%) in histologically normal colorectal mucosa from individuals with concurrent cancer compared to mucosa from individuals without colorectal cancer (12%), suggesting the existence of a 'field defect' involving methylated EVL/hsa-miR-342. Furthermore, reconstitution of hsa-miR-342 in the colorectal cancer cell line HT-29 induced apoptosis, suggesting that this microRNA could function as a proapoptotic tumor suppressor. In aggregate, these results support a novel mechanism for silencing intronic microRNAs in cancer by epigenetic alterations of cognate host genes.
- Publication
Oncogene, 2008, Vol 27, Issue 27, p3880
- ISSN
1476-5594
- Publication type
Journal Article
- DOI
10.1038/onc.2008.10