Journal
BRITISH JOURNAL OF CANCER
Volume 104, Issue 11, Pages 1770-1778Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/bjc.2011.82
Keywords
miR-34b/c; miR-148a; methylation; faeces; CRC
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Funding
- University Hospital Tor Vergata, University of Rome
- International Italian Government University
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BACKGROUND: MicroRNAs are tiny non-coding small endogenous RNAs that regulate gene expression by translational repression, mRNA cleavage and mRNA inhibition. The aim of this study was to investigate the hypermethylation of miR-34b/c and miR-148a in colorectal cancer, and correlate this data to clinicopathological features. We also aimed to evaluate the hypermethylation of miR-34b/c in faeces specimens as a novel non-invasive faecal-DNA-based screening marker. METHODS: The 5-aza-2'-deoxycytidine treatment and methylation-specific PCR were carried out to detect the hypermethylation of miR-34b/c and miR-148a. RESULTS: The miR-34b/c hypermethylation was found in 97.5% (79 out of 82) of primary colorectal tumours, P = 0.0110. In 75% (21 out of 28) of faecal specimens we found a hypermethylation of miR-34b/c while only in 16% (2 out of 12) of high-grade dysplasia. In addition, miR-148a was found to be hypermethylated in 65% (51 out of 78) of colorectal tumour tissues with no significant correlation to clinicopathological features. However, a trend with female gender and advanced age was found, P = 0.083. We also observed a trend to lower survival rate in patients with miR-148a hypermethylation with 10-year survival probability: 48 vs 65%, P = 0.561. CONCLUSIONS: These findings show that aberrant hypermethylation of miR-34b/c could be an ideal class of early screening marker, whereas miR-148a could serve as a disease progression follow-up marker. British Journal of Cancer (2011) 104, 1770-1778. doi:10.1038/bjc.2011.82 www.bjcancer.com (C) 2011 Cancer Research UK
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