miR-367 promotes proliferation and stem-like traits in medulloblastoma cells

Autor(es)

Kaid, Carolini ; Silva, Patricia B. G. ; Cortez, Beatriz A. ; Rodini, Carolina O. ; Semedo-Kuriki, Patricia ; Okamoto, Oswaldo K.

• Tipo de documento: Artigo Científico
• Fonte: CANCER SCIENCE; v. 106, n. 9, p. 8-pg., 2015-09-01.

Resumo

In medulloblastoma, abnormal expression of pluripotency factors such as LIN28 and OCT4 has been correlated with poor patient survival. The miR-302/367 cluster has also been shown to control self-renewal and pluripotency in human embryonic stem cells and induced pluripotent stem cells, but there is limited, mostly correlational, information about these pluripotency-related miRNA in cancer. We evaluated whether aberrant expression of such miRNA could affect tumor cell behavior and stem-like traits, thereby contributing to the aggressiveness of medulloblastoma cells. Basal expression of primary and mature forms of miR-367 were detected in four human medulloblastoma cell lines and expression of the latter was found to be upregulated upon enforced expression of OCT4A. Transient overexpression of miR-367 significantly enhanced tumor features typically correlated with poor prognosis; namely, cell proliferation, 3-D tumor spheroid cell invasion and the ability to generate neurosphere-like structures enriched in CD133 expressing cells. A concurrent downregulation of the miR-367 cancer-related targets RYR3, ITGAV and RAB23, was also detected in miR-367-overexpressing cells. Overall, these findings support the pro-oncogenic activity of miR-367 in medulloblastoma and reveal a possible mechanism contributing to tumor aggressiveness, which could be further explored to improve patient stratification and treatment of this important type of pediatric brain cancer. (AU)

• Processo FAPESP: 11/10001-9 - Contribuição das células-tronco mesenquimais ao desenvolvimento tumoral
• Beneficiário: Carolina de Oliveira Rodini
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 13/17566-7 - Fator de pluripotência OCT4A e agressividade de meduloblastoma humano
• Beneficiário: Patrícia Benites Gonçalves da Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 10/52686-5 - Fator de transcrição E2F2 e expressão de proto-oncogenes em células-tronco embrionárias humanas
• Beneficiário: Oswaldo Keith Okamoto
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 13/02983-1 - Expressão de hsa-miR-367 e agressividade de meduloblastoma humano
• Beneficiário: Carolini Kaid Dávila
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 14/10519-6 - Via de sinalização hippo e divisão assimétrica de células-tronco tumorais derivadas de meduloblastoma humano
• Beneficiário: Beatriz de Araujo Cortez
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 13/08028-1 - CEGH-CEL - Centro de Estudos do Genoma Humano e de Células-Tronco
• Beneficiário: Mayana Zatz
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs