miRNAs and melanoma: how are they connected?

• Grant number: 11/11299-1
• Support Opportunities: Regular Research Grants - Publications - Scientific article
• Duration: July 01, 2011 - December 31, 2011
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Miriam Galvonas Jasiulionis
• Grantee: Miriam Galvonas Jasiulionis
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated research grant: 06/61293-1 - DNA methylation contribution to carcinogenesis, AP.JP

Abstract

miRNAs are non-coding RNAs that bind to mRNA targets and disturb their stability and/or translation, thus acting in gene post-transcriptional regulation. It is predicted that over 30% of mRNAs are regulated by miRNAs. Therefore these molecules are considered essential in the processing of many biological responses, such as cell proliferation, apoptosis and stress responsiveness. As miRNAs participate of virtually all cellular pathways, their deregulation is critical to cancer development. Consequently, loss or gain of miRNAs function may contribute to tumor progression. Little is known about the regulation of miRNAs and understanding the events that lead to changes in their expression may provide new perspectives for cancer treatments. Evidences have shown that epigenetic events are involved in miRNA expression. In fact, both miRNA expression and epigenetic mechanisms can suffer influence of each other. In this regard, miRNAs and epigenetics are extremely linked. Epigenetic studies regulatory mechanisms related with activity and inheritance of gene expression that is independent of modifications in nucleotide sequence. The main epigenetic events are: DNA methylation and post-translational modifications in histones. Epigenetic mechanisms are also tightly correlated with tumorigenesis since different tumors show alteration in global DNA methylation pattern, changes in histone tail marks and divergent expression of enzymes responsible for such events. Among distinct types of cancers, melanoma has special implications. It is characterized as a complex disease, originated from a malignant transformation of melanocytes. Despite being rare, its metastatic form is usually incurable, which makes melanoma the major death cause of all skin cancers. Five-year survival rate for advanced melanoma is estimated in less than 10% of affected patients. Some molecular pathways are frequently disrupted in melanoma, and miRNAs probably have a decisive role on these alterations. Therefore, this review aims to discuss new findings about miRNAs in melanoma fields, underlying epigenetic processes, and also to argue possibilities of using miRNAs in diagnosis and therapy on that cancer. (AU)