MicroRNAs are small non coding RNA molecules that are generated within cells and play a role in post transcriptional gene regulation. It is becoming clear that aberrant expression of miRNAs has a role in cancerous transformation these and progression. Sev eral miRNA profiling studies in melanoma were published until now, but the picture emerging from these works is far from being clear. A large miRNA cluster was recently shown to be down regulated in ovarian cancer, and eight miRNAs in this clus ter were identified as potential tumor suppressor genes. Lately, this cluster was also implicated in gastro intestinal stromal tumors and in gliomas. Additionally, mir 127 from this cluster was shown to have tumor sup pressor function in a bladder cancer model.

This miRNA cluster lies within a parentally imprinted chromo somal area designated Dlk1 Gtl2 in Inhibitors,Modulators,Libraries mouse or Dlk Dio3 in human. This area is of great developmental import ance, exemplified by severe phenotypes associated with altered dosages of the genes within it in mice and humans. The regulation of imprinting in this chromosomal locus is thought to be mediated, at least to some extent, by an intergenic differentially methylated region that is located centromeric to the imprinted region. Indeed, this region was shown to be differentially methy lated during embryonic development in humans. Another regulatory region, located more telomeric, is designated MEG3 DMR. Human studies performed on infants with uniparental Inhibitors,Modulators,Libraries dysomy of each of these DMRs imply that the IG DMR and the MEG3 DMR function as imprinting control centers in the placenta and the body, re spectively, with a hierarchical interaction for the methyla tion pattern in the body governed by the IG DMR.

In mouse, deletion of IG DMR from Inhibitors,Modulators,Libraries the maternally inherited chromosome causes bi directional loss of imprinting of all genes in the cluster. A meticu lous characterization of all transcripts in this mouse locus demonstrated that the miRNAs within Inhibitors,Modulators,Libraries this cluster were ex clusively expressed from the maternal chromosome. The other maternally expressed transcripts in this region were found to have exclusive pat terns of expression, being detected only in brain, testis and skin. Very recently, the expression of miRNAs from this region was found to be essential for maintaining full pluripotency of induced pluripotent stem cells.

Along the years, there have been few descriptions of chromosomal abnormalities in melanoma samples. 15 years ago, the translocation t was found in several of 20 melanoma samples taken from patients, and more than a decade later this chromo somal region was again found Inhibitors,Modulators,Libraries to be aberrant in some melanoma cell lines. Recently, Zhang et al. deter mined DNA copy number abnormalities in 283 miRNA genes in three different cancer types using selleck chemicals comparative genomic hybridization, and showed loss of hetrozygocity of the 14q32 miRNA cluster in 20% of the melanoma cell lines examined.