A regulação do MIR-10B e do MIR-603 pelas proteínas HMGA tem papel crítico na transformação de células da tireóide

Abstract

HMGA overexpression, other than to be a feature of human malignant neoplasias, has a causal role in cell transformation. Then, the aim of our study has been to investigate the miRNAs regulated by the HMGA proteins in the process of cell transformation analyzing the miRNA expression profile of v-ras-ki oncogenetransformed thyroid cells expressing or not HMGA proteins. We demonstrate that, among the miRNAs regulated by cell transformation, there are miR-10b, miR-21, miR-125b, miR-221 and miR-222 that are positively and miR-34a and miR-603 that are negatively regulated, by HMGA expression. Then, we focused our attention on the miR-10b and miR-603 whose expression appeared to be dependent on the presence of the HMGA proteins also in other cell systems. We found that miR-10b is able to target the PTEN gene, whereas miR-603 targets CCND1 and CCND2 genes. Moreover, functional studies showed that miR-10b and miR-603 were able to regulate positively and negatively, respectively, cell proliferation and migration suggesting a role of their deregulation in thyroid cell transformation.