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Previous issue date: 2012-08-17 / 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. / A super express?o das prote?nas HMGA (High Mobility Group A) al?m de ser uma caracter?stica de neoplasias humanas malignas tem uma papel essencial na transforma??o celular. O objetivo deste trabalho foi identificar os miRNAs associados as prote?nas HMGA no processo de transforma??o celular, analisando perfil de express?o de microRNAs (miRNAs) em c?lulas da tire?ide transformadas com o oncogene v-ras-ki, expressando ou n?o as prote?nas HMGA. Entre os miRNAs regulados pela transforma??o celular, observou-se que o miR-10b, miR-21, miR- 125b, miR-221 e o miR-222 s?o positivamente e o miR-34a and miR-603 s?o negativamente regulados pela express?o das prote?nas HMGA. Assim focamos nossa atencao no miR-10b e no miR-603 cuja express?o parece ser dependente da presen?a das prote?nas HMGA tamb?m em outros sistemas celulares. Igualmente, foi demonstrado que CCND1 e CCND2 s?o alvos do miR-603, e PTEN alvo do miR- 10b. Al?m disso, os estudos funcionais demonstraram que o miR-10b e o miR-603 s?o capazes de regular positiva e negativamente a prolifera??o celular e migra??o, sugerindo um papel da sua desregula??o na transforma??o de c?lulas da tire?ide.
| Identifer | oai:union.ndltd.org:IBICT/oai:tede2.pucrs.br:tede/2685 |
| Date | 17 August 2012 |
| Creators | Freitas, Paula M?ssnich de |
| Contributors | Machado, Denise Cantarelli |
| Publisher | Pontif?cia Universidade Cat?lica do Rio Grande do Sul, Programa de P?s-Gradua??o em Gerontologia Biom?dica, PUCRS, BR, Instituto de Geriatria e Gerontologia |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da PUC_RS, instname:Pontifícia Universidade Católica do Rio Grande do Sul, instacron:PUC_RS |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 4438661476953179033, 500, 600, 2296420844541114010 |
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