Abstract 3167: miR-138 and its role in melanoma progression

Abstract

Abstract miRNAs are non-coding RNAs that bind to mRNA targets preventing their translation. It is predicted that over 30% of mRNAs are regulated by miRNAs. Therefore these molecules are considered essential to many biological responses, such as cell proliferation, apoptosis and stress responsiveness. Loss or gain of miRNAs function contributes to development of many diseases, included cancer. Melanoma rises from malignant transformation of melanocytes. Despite being rare, it is responsible for the greatest number of deaths promoted by all skin cancers. One reason for this scenario is that melanoma metastatic is usually incurable. To determine the role of miRNAs in melanoma progression, the expression of several miRNAs were evaluated in a murine model that mimics different stages of the genesis of this tumor. In that model, several cell lines were obtained after submitting melan-a melanocytes to sequential cycles of anchorage blockade. Among miRNAs in which expression were altered, miR-138 has decreased expression in intermediate phases of melanoma genesis and was selected for further investigation. It was verified that mRNA of p53, Ezh2, MyoD and Sirt-1 are putative targets of miR-138. Interestingly, these mRNAs also have inverse expression of miR-138 in the distinct lineages of this model. Luciferase assay was done to confirm if miR-138 directly regulate such mRNAs. Super expression of miR-138 in the cell lineages that have lower levels of this miRNA was also induced. Functional experiments assessing proliferation rate, migration and invasiveness capacity in these cells expressing ectopic miR-138 were performed. The results indicate that miR-138 deregulation is an important event of melanoma progression. The targets of this miRNA are key components in pathways frequently disrupted in cancer, like cell cycle and apoptosis control, epithelial to mesenchymal transition regulation, and differentiation process. Thus, miR-138 represents a strong candidate to therapeutic target. The exploration of its role can contribute to improve the comprehension about melanoma progression and elucidate new ways of interventions against cancer. Supported by FAPESP. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3167. doi:1538-7445.AM2012-3167