Metastasis: Micro silencing
Hypermethylation of microRNAs could lead to their deregulated expression, which has been implicated in the development of tumor metastases.
The deregulated expression of microRNAs has been implicated in the development of tumour metastases. New evidence from Manel Esteller and colleagues indicates that hypermethylation of microRNAs could be responsible for this deregulated expression.
Evidence that non-coding microRNAs are subject to epigenetic regulation led Esteller and colleagues to ask whether a microRNA hypermethylation profile is evident in human tumours. Three human metastatic cancer cell lines were treated with the DNA methylation inhibitor 5-aza-2'-deoxycytidine. RNA analyses of the treated and untreated cells showed that 57 of 389 microRNAs showed increased expression in the presence of 5-aza-2'-deoxycytidine, and 27 of these were embedded in a canonical CpG island — stretches of DNA that are commonly associated with DNA methylation. MiR-148a, miR-34b/c and miR-9 were specifically hypermethylated in cancer cells and their re-expression in these cells suppressed tumour growth, motility and metastasis in xenograft models. This correlated with reduced expression of some of their known target genes, including MYC and E2F3. Importantly, the authors also showed that hypermethylation of these microRNAs correlated with the appearance of lymph node metastasis in 207 primary human tumour samples.
If verified, such information could be used to predict patients that are more likely to develop metastasis. These findings also indicate that drugs that lead to DNA demethylation might be useful for the treatment of metastatic disease.
Nicola McCarthy
References
- Lujambio, A. et al. A microRNA DNA methylation signature for human cancer metastasis. Proc. Natl Acad. Sci. USA 105, 13556–13561 (2008) | Article | PubMed |
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