The High Mobility Group A proteins contribute to thyroid cell transformation by regulating miR-603 and miR-10b expression

Abstract

The overexpression of the HMGA1 proteins is a feature of human malignant neoplasias and has a causal role in cell transformation. The aim of our study has been to investigate the microRNAs (miRNAs or miRs) regulated by the HMGA1 proteins in the process of cell transformation analyzing the miRNA expression profile of v-ras-Ki oncogene-transformed thyroid cells expressing or not HMGA1 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 HMGA1 expression. Then, we focused our attention on the miR-10b and miR-603 whose expression was dependent on the presence of HMGA1 also in other cell systems. We found that miR-10b is able to target the PTEN gene, whereas miR-603 targets the CCND1 and CCND2 genes coding for the cyclin D1 and cyclin D2 proteins, respectively. Moreover, functional studies showed that miR-10b and miR-603 regulate positively and negatively, respectively, cell proliferation and migration suggesting a role of their dysregulation in thyroid cell transformation.