Epigenetic regulation of miRNA genes and their role in human melanomas

Abstract

Melanoma is a leading cause of death from cancers in the USA. While exposure to UV radiation has long been identified as a primary risk factor for melanoma, molecular mechanisms directly linking UV radiation to the development of melanoma, especially metastatic melanoma, are poorly understood. Besides abnormality in several signal transduction pathways important for normal melanocyte development, a number of ncRNAs, including miRNAs, are emerging as important causal factors to melanoma initiation and progression. The recent discovery of altered patterns of epigenetic regulation in ncRNA genes adds further complexity. Since miRNA precursor genes are usually nested within other protein-coding genes, the abnormal regulation of these protein-coding genes by epigenetic mechanisms is expected to cause aberrant regulation of the miRNA target genes. We discuss recent findings that link epigenetic regulation of ncRNA genes to melanoma, and speculate on a possible connection between UV irradiation and epigenetic regulation that might be important for this disease.