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Abstract 2779: miR-142-3p as a regulator of RAC1 and a prognostic factor in melanoma

Tumor Biology(2019)

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Abstract
In order to identify miRNAs able to distinguish melanoma patients with good or poor prognosis, the expression profile of a panel of miRNAs evaluated in primary melanoma samples from 65 patients was compared to clinicopathological data from these patients (Breslow’s depth, mitotic counts, metastasis progression and survival). The miR-142-3p was identified as presenting at least 2-fold reduced expression in melanoma samples from patients with poor prognosis for 3 of 4 clinical parameters analyzed compared to melanoma samples from patients with good prognosis. The miR-142-3p expression was validated by RT-qPCR in primary human melanoma samples, confirming a significant lower expression in melanoma patients with poor prognosis compared to those with good prognosis. Searching for miR-142-3p mRNA targets in melanoma, the gene expression profile was analyzed by gene microarrays in a wild type and miR-142-3p overexpressing melanoma cell line. RAC1, ITGB8 e GNB2 were found as potential targets of this miRNA. Protein expression analyses in melanoma cell lines overexpressing the miR-142-3p reinforced the regulation of RAC1 by this miRNA. Functional assays showed that the overexpression of miR-142-3p leads to a reduced migratory ability compared to control cells, indicating its role in cell migration process. Finally, multivariate COX analyses demonstrated that high levels of RAC1 and reduced levels of miR-142-3p predict poor progression-free survival of melanoma patients, revealing these molecules as potential prognostic biomarkers for melanoma patients. Supported by FAPESP, CNPQ and CAPES Short title: miR-142-3p as a prognostic factor in melanoma Note: This abstract was not presented at the meeting. Citation Format: Adriana T. Cruz, Julia A. Morata, Ana C. Monteiro, Ana Luisa P. Ayub, Roseli S. Soares, Andre Fujita, Fernando Andrade, Victor Tron, Miriam G. Jasiulionis. miR-142-3p as a regulator of RAC1 and a prognostic factor in melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2779.
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melanoma,rac1
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