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Regulation between hsa-miR-4719 and nucleostemin in meduloblastoma

Grant number: 17/04325-2
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2017
Effective date (End): July 10, 2018
Field of knowledge:Biological Sciences - Genetics
Principal Investigator:Oswaldo Keith Okamoto
Grantee:Leonardo da Costa Carvalheira
Home Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The POU5F1 gene is responsible for expression of the OCT4 protein, which is found with higher expression than normal in embryonic and tumor stem cells, and is related to maintenance of the undifferentiated state. Our group detected a correlation between increased POU5F1 expression and decreased survival of patients with medulloblastoma, increased tumor aggressiveness by faster cell growth, increased cell invasion, increased tumorigenicity, and increased propensity to metastasize. It was also observed that increased expression of this protein affected the levels of other transcripts as micro RNAs (miRNA), long chain non-coding RNAs, nucleolar RNAs, and other proteins. The hsa-miRNA-367, which was present in the lineages less express than normal, was best studied among these transcripts and it expression in vitro and in vivo has presented greater viability in medulloblastoma cells. It is then deduced that the miRNAs found with affected expression in the lineages may affect the tumor aggressiveness in medulloblastoma. In addition, it lacks information on the molecular mechanisms of OCT4 acting in the increase of medulloblastoma aggressiveness in the literature. So it comes the importance of this project, which intends to study, of the implications of the concentration beyond normal of OCT4, the hsa-miRNA-4719, which has less than normal expression in medulloblastoma lineages, and its relation with nucleostemine, a possible target that is overexpressed in the same lineages, and which has overexpression also in other tumors such as glioblastomas and neuroblastomas, and in neural stem cells, but not in its differentiated progeny (TSAI and MCKAY, 2002). If the miRNA and the protein do not have a direct relation, we intend to study the mechanisms of nucleostemine in medulloblastoma, as there is also the possibility of its expression being directly controlled by the transcripts of the POU5F1 gene. (AU)