Expression and mechanism of hsa-miR-367 in neurogenesis and aggressiveness of human medulloblastoma

• Grant number: 16/25285-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2017
• End date: March 31, 2018
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Oswaldo Keith Okamoto
• Grantee: Dione Oliveira Jordan
• Host Institution: Instituto de Biociências (IB). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Medulloblastoma is an embryonic tumor from Central Nervous System (CNS) and the most common among children from zero to four years old. The origin of this malignat pediatric tumor is still undefined, but believed to be derived from cells with stem cells characteristics during the development of cerebellum. This tumor is classified as being highly aggressive, with rapid growth and capacity to spread through the CNS generating local metastases. The current treatments are not effective then tumor recurrence and sequels are common, therefore medulloblastoma is one of the main cause of child morbidity. Recent studies demonstrate that certain tumor cells express genes typically overexpressed in stem cells contributing to enhance aggressiveness and worse prognosis. Several factors can induce the phenotype of stem cells in tumors, amid them the miRNAs has been indicated as relevant factors to maintenance of pluripotency and cell reprogramming, thereby they can be useful markers and even noninvasive therapeutic targets. miR-367 is overexpressed in embryonic cells, has already been efficiently used in cell reprogramming and its contribution as an oncogenic factor is verified, however the mechanisms that allow this contribution and its direct regulation to cell differentiation processes are still not fully elucidated. Therefore, in this project, we will investigate this miRNA participation in neurogenesis and its relationship with aggressiveness in human medulloblastoma trying to understand the mechanisms that induce and maintain the phenotype of stem cells in tumors. (AU)