Oncotarget

Research Papers:

High OCT4A levels drive tumorigenicity and metastatic potential of medulloblastoma cells

Patrícia Benites Gonçalves da Silva, Márcia Cristina Teixeira dos Santos, Carolina Oliveira Rodini, Carolini Kaid, Márcia Cristina Leite Pereira, Gabriela Furukawa, Daniel Sanzio Gimenes da Cruz, Mauricio Barbugiani Goldfeder, Clarissa Ribeiro Reily Rocha, Carla Rosenberg and Oswaldo Keith Okamoto _

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Oncotarget. 2017; 8:19192-19204. https://doi.org/10.18632/oncotarget.15163

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Abstract

Patrícia Benites Gonçalves da Silva1, Márcia Cristina Teixeira dos Santos1, Carolina Oliveira Rodini1, Carolini Kaid1, Márcia Cristina Leite Pereira1, Gabriela Furukawa1, Daniel Sanzio Gimenes da Cruz2, Mauricio Barbugiani Goldfeder3, Clarissa Ribeiro Reily Rocha4, Carla Rosenberg1, Oswaldo Keith Okamoto1

1Centro de Pesquisa sobre o Genoma Humano e Células-Tronco, Departamento de Genética e Biologia Evolutiva, Instituto de Biociências, Universidade de São Paulo, São Paulo, SP, Brazil

2Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, São Paulo, SP, Brazil

3Laboratório de Bioquímica e Biofísica, Instituto Butantan, São Paulo, SP, Brazil

4Departmento de Microbiologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brazil

Correspondence to:

Oswaldo Keith Okamoto, email: [email protected]

Keywords: OCT4A, POU5F1, LIN28A, medulloblastoma, aggressiveness

Received: May 26, 2016     Accepted: January 22, 2017     Published: February 07, 2017

ABSTRACT

Medulloblastoma is a highly aggressive pediatric brain tumor, in which sporadic expression of the pluripotency factor OCT4 has been recently correlated with poor patient survival. However the contribution of specific OCT4 isoforms to tumor aggressiveness is still poorly understood. Here, we report that medulloblastoma cells stably overexpressing the OCT4A isoform displayed enhanced clonogenic, tumorsphere generation, and invasion capabilities. Moreover, in an orthotopic metastatic model of medulloblastoma, OCT4A overexpressing cells generated more developed, aggressive and infiltrative tumors, with tumor-bearing mice attaining advanced metastatic disease and shorter survival rates. Pro-oncogenic OCT4A effects were expression-level dependent and accompanied by distinct chromosomal aberrations. OCT4A overexpression in medulloblastoma cells also induced a marked differential expression of non-coding RNAs, including poorly characterized long non-coding RNAs and small nucleolar RNAs. Altogether, our findings support the relevance of pluripotency-related factors in the aggravation of medulloblastoma traits classically associated with poor clinical outcome, and underscore the prognostic and therapeutic value of OCT4A in this challenging type of pediatric brain cancer.


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PII: 15163