Polysome Profiling of a Human Glioblastoma Reveals Intratumoral Heterogeneity

Autor(es):Mostrar menos -

Sulla Lupinacci, Fernanda Cristina ; Kuasne, Hellen ; Roffe, Martin ; Vassalakis, Julia Avian ; da Silva, Fernanda Ferreira ; Santos, Tiago Goss ; Andrade, Victor Piana ; Sanematsu, Paulo ; Martins, Vilma Regina ; Rogatto, Silvia Regina ; Maroso Hajj, Glaucia Noeli

• Tipo de documento: Artigo Científico
• Fonte: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 20, n. 9, p. 14-pg., 2019-05-01.

Resumo

Glioblastoma (GBM) is one of the most aggressive cancers, with median survival of less than 2 years. Despite of considerable advance in molecular classification of GBMs, no improvements in therapy have been described. The scenario is further complicated by tumor heterogeneity and the relationship among genetic, transcriptional and functional findings. Classically, gene expression has been evaluated by steady-state mRNA, however, this does not take translational control into consideration, which contributes considerably to the composition of the proteome. In this study, we evaluated the transcriptomic and translatomic signature of a GBM obtained from a single patient focusing in tumor heterogeneity. In a sampling of eight fragments, we investigated the translation rates, mTORC1 and ERK1/2 pathways and identified both total and polysome associated mRNAs. An increased translation rate was observed in fragments with high-grade histological features. High-grade histology was also associated with the expression of genes related to extracellular matrix (ECM) and angiogenesis, in both transcriptomes and translatomes. However, genes associated with epithelial to mesenchymal transition and stress response, were observed only in translatomes from high-grade fragments. Overall, our results demonstrate that isolation of translated mRNA can be used to identify biomarkers and reveal previously unrecognized determinants of heterogeneity in GBMs. (AU)

• Processo FAPESP: 15/15451-3 - Estudo da Regulação e Função da família das RSKs em Glioblastomas
• Beneficiário: Martín Roffé
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/17796-6 - Controle traducional no câncer - Parte II
• Beneficiário: Glaucia Noeli Maroso Hajj
• Modalidade de apoio: Auxílio à Pesquisa - Regular