microRNAs (miRNAs) are small, non-coding RNAs with critical roles in fine-tuning a wide array of biological processes including development, metabolism, and homeostasis. miRNAs expression, similarly to that of protein-coding genes, is regulated by multiple transcriptional networks as well as the epigenetic machinery. miRNA genes can be epigenetically regulated by DNA methylation or specific histone modifications. In addition, miRNAs can themselves repress key enzymes that drive epigenetic remodeling, generating regulatory circuits that have a significant effect in the transcriptional landscape of the cell. Recent evidences also suggest that miRNAs can directly modulate gene transcription in the nucleus through the recognition of specific target sites in promoter regions. Given the widespread distribution of epigenetic marks and miRNA target sites in the genome, the regulatory circuits linking both mechanisms are likely to have a major impact in genome transcription and cell physiology. Not surprisingly, tumor-associated aberrations in the miRNA or epigenetic machineries are widely distributed in human cancer, and we are just starting to understand their relevance in diagnosis, prognosis or therapy.
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