Expression of hsa-miR-367 and aggressiveness of human medulloblastoma

Author(s)

Carolini Kaid Davila

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB)
• Defense date: 2015-01-30

Examining board members

Oswaldo Keith Okamoto; Adriana Miti Nakahata; Eloiza Helena Tajara da Silva

• Advisor: Oswaldo Keith Okamoto

Abstract

Medulloblastoma is the most common malignant brain tumor in children aged four and younger, and is the leading cause of infant morbidity and mortality. Several studies have reported the activation of stem cell genes leading to more primitive and aggressive characteristics in tumor cell often associated with unfavorable clinical prognosis. Cell reprogramming, stimulated by tumor microenvironment factors, might induce tumor stem cells phenotype. Recent researches suggest an involvement of miR-367 in fibroblasts reprogramming into pluripotent state, as well as a correlation with poor prognosis in some cancers. In this study, we observed a possible functional role of miR-367 in medulloblastoma aggressiveness. Four different medulloblastoma cell lines, Daoy, D283-Med, CHLA-01-Med and USP-13-Med showed low rates of pri-miR-367 and mature miR-367 expression. Overexpression of miR-367 down-regulated the protein levels of its target RYR3 and of two bioinformatically predicted transcript targets encoding ITGAV and RAB23, which are involved in cancer in CHLA-01-Med and USP-13 Med cell lines. Furthermore, transfection with the miRNA mimic significantly increased cell proliferation and the percentage of cells observed in S + G2 / M phase of the cell cycle. Although the sensitivity to cisplatin treatment was not changed after overexpression of miR-367, the ability to generate neurospheres in vitro was significantly increased. This last result can be related to clinical ones because cells from medulloblastoma patients with low survival show great ability to generate neurospheres. In sum, these findings suggest a pro-oncogenic role to miR-367, which can affect medulloblastoma aggressiveness by cell proliferation and neural stem cells positive modifications (AU)

• FAPESP's process: 13/02983-1 - Expression of hsa-miR-367 and aggressiveness of human medulloblastoma
• Grantee: Carolini Kaid Dávila
• Support Opportunities: Scholarships in Brazil - Master