MicroRNAs involved in melanoma genesis and progression

• Grant number: 12/08776-5
• Support type: Regular Research Grants
• Duration: November 01, 2012 - October 31, 2015
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Miriam Galvonas Jasiulionis
• Grantee: Miriam Galvonas Jasiulionis
• Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

Non-coding RNAs are RNA molecules presenting structural, enzymatic and regulatory functions. Among those with regulatory function are miRNAs, which correspond to small RNAs constituted by approximately 22 nucleotides. MicroRNAs (miRNAs) are able to bind to target messenger RNAs (mRNAs) and block their translation. More than 60% of mRNAs are estimated to be regulated by miRNAs and, thus, these molecules are considered fundamental in the control of several biological processes. Changes in miRNA expression contribute to loss of cellular homeostasis and may favor the development of different patological states. Little is known about the mechanisms related to miRNA control and a better comprehension of the events leading to alterations in their expression may give us new perspectives to the treatment of pathologies, such as cancer. Cutaneous melanoma is the most lethal type of skin cancer and develops from the malignant transformation of melanocytes, as result of complex interactions between genetic and epigenetic factors. DNA methylation and histone modifications are among the most studied epigenetic mechanisms. Alterations in epigenetic mechanisms may promote modifications in miRNA expression profile, contributing to tumor progression. A murine model of melanocyte malignant transformation was developed in our laboratory, in which cell lines representing differents phenotypes associated to melanoma were established after submitting a non-tumorigenic melanocyte lineage, melan-a, to sequential cycles of anchorage blockade. In this context, this study aims to identify miRNAs differentiatly expressed along melanocyte malignant transformation; determine cellular pathways under miRNA control; determine miRNAs under epigenetic control; identify miRNAs related to response to treatment; identify miRNAs which may be used as markers of melanoma progression and/or targets to novel therapeutical strategies. (AU)