Epigenetic mechanisms of HOX gene modulation in medulloblastoma
| Grant number: | 11/18664-7 |
| Support type: | Scholarships in Brazil - Doctorate |
| Effective date (Start): | December 01, 2011 |
| Effective date (End): | August 31, 2015 |
| Field of knowledge: | Biological Sciences - Genetics |
| Principal Investigator: | Aparecida Maria Fontes |
| Grantee: | Ricardo Bonfim Silva |
| Home Institution: | Hemocentro de Ribeirão Preto. Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da USP (HCMRP). Secretaria da Saúde (São Paulo - Estado). Ribeirão Preto , SP, Brazil |
| Associated scholarship(s): | 14/13546-4 - Regulation of Skp2 by the Interleukin-7/STAT3 axis in T-cell acute lymphoblastic leukemia, BE.EP.DR |
Abstract Over the last 10-15 years, it has been recognized that development is a key for understanding tumor evolution. Many genes that control development are altered in cancer cells and have implications in neoplastic transformation. In this respect, homeobox genes are primordial for development and their epigenetic deregulation is being progressively associated with tumor progression in various types of cancer. However, little is understood about how Hox genes contribute to the development of medulloblastoma. In medulloblastoma, it has been demonstrated that some Hox genes are altered, although the mechanisms involved in this deregulation have not been elucidated. It is known that lncRNA Evf-2 is an lncRNA typical of the central nervous system, that it is deregulated in some neuronal disorders and that specifically affects the transcription of protein homeodomains, which are proteins encoded by the Hox genes. Therefore, this led us to raise the hypothesis that deregulation of Hox genes may be associated with tumor evolution in medulloblastoma and that these mechanisms may involve interaction of lncRNA Evf-2. Thus, the objective of this project is to investigate the role of lncRNA Evf-2 in the modulation of Hox genes and in the metastatic potential of medulloblastoma. The methodology involved will be divided into three parts: (1) to investigate whether lncRNA Evf-2 and the Hox genes are deregulated in two meduloblastoma lines (Uw402 and Uw473); (2) to investigate the effect of the overexpression of the lncRNA Evf-2 in the expression of Hox genes, in the migratory and invasive in vitro potential and in the in vivo metastatic potential; (3) functional assays directed to investigate whether silencing of Hox genes have an in vivo and in vitro effect on the metastatic potential of medulloblastoma cells that overexpress the lncRNA Evf-2. | |