Methylation of human microRNA genes in normal and neoplastic cells.

MicroRNAs (miRNAs) are small RNA molecules that control gene expression by inhibition of protein translation or degradation of cognate target mRNAs. Eventhough strict Even though strict developmental and tissue-specific regulation appears to be critical for miRNA function, very little is known about the mechanisms governing miRNA gene expression. Several recent studies have shown that miRNA genes can regulated DNA methylation and other epigenetic mechanisms. The observation of altered miRNA gene methylation patterns in human cancers also suggested that miRNA gene methylation is functional relevant for tumorigenesis. We have now performed a comprehensive analysis of miRNA genes and found that about half of these genes are associated with CpG islands and thus represent candidate targets of the DNA methylation machinery An expanded analysis of several miRNA-associated CpG islands in five cell lines indicated that miRNA gene methylation is detectable at high frequencies, both in normal and malignant cells. Possible explanations for this phenomenon include the specific structure of miRNA genes and/or their requirement for strict expression regulation.