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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

miR-124,-128, and-137 Orchestrate Neural Differentiation by Acting on Overlapping Gene Sets Containing a Highly Connected Transcription Factor Network

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Autor(es):
Santos, Marcia C. T. [1, 2] ; Tegge, Allison N. [3, 4] ; Correa, Bruna R. [5, 2] ; Mahesula, Swetha [1] ; Kohnke, Luana Q. [1, 2] ; Qiao, Mei [2] ; Ferreira, Marco A. R. [4] ; Kokovay, Erzsebet [1] ; Penalva, Luiz O. F. [1, 2]
Número total de Autores: 9
Afiliação do(s) autor(es):
[1] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 - USA
[2] Univ Texas Hlth Sci Ctr San Antonio, Childrens Canc Res Inst, San Antonio, TX 78229 - USA
[3] Virginia Tech, Dept Comp Sci, Blacksburg, VA - USA
[4] Virginia Tech, Dept Stat, Blacksburg, VA - USA
[5] Hosp Sirio Libanes, Ctr Oncol Mol, Sao Paulo - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: Stem Cells; v. 34, n. 1, p. 220-232, JAN 2016.
Citações Web of Science: 28
Resumo

The ventricular-subventricular zone harbors neural stem cells (NSCs) that can differentiate into neurons, astrocytes, and oligodendrocytes. This process requires loss of stem cell properties and gain of characteristics associated with differentiated cells. miRNAs function as important drivers of this transition; miR-124, -128, and -137 are among the most relevant ones and have been shown to share commonalities and act as proneurogenic regulators. We conducted biological and genomic analyses to dissect their target repertoire during neurogenesis and tested the hypothesis that they act cooperatively to promote differentiation. To map their target genes, we transfected NSCs with antagomiRs and analyzed differences in their mRNA profile throughout differentiation with respect to controls. This strategy led to the identification of 910 targets for miR-124, 216 for miR-128, and 652 for miR-137. The target sets show extensive overlap. Inspection by gene ontology and network analysis indicated that transcription factors are a major component of these miRNAs target sets. Moreover, several of these transcription factors form a highly interconnected network. Sp1 was determined to be the main node of this network and was further investigated. Our data suggest that miR-124, -128, and -137 act synergistically to regulate Sp1 expression. Sp1 levels are dramatically reduced as cells differentiate and silencing of its expression reduced neuronal production and affected NSC viability and proliferation. In summary, our results show that miRNAs can act cooperatively and synergistically to regulate complex biological processes like neurogenesis and that transcription factors are heavily targeted to branch out their regulatory effect. (AU)

Processo FAPESP: 11/51588-2 - Caracterização funcional da proteína LIN28 no processo de tumorigênese do sistema nervoso central
Beneficiário:Márcia Cristina Teixeira dos Santos
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 12/22950-8 - Caracterização funcional das proteínas de ligação ao RNA Lin28 e Msi1 nos processos de neurogênese
Beneficiário:Márcia Cristina Teixeira dos Santos
Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
Processo FAPESP: 13/25483-4 - Identificação e análise funcional de proteínas de ligação a RNA associadas com o desenvolvimento do glioblastoma multiforme
Beneficiário:Bruna Renata Silva Corrêa
Linha de fomento: Bolsas no Exterior - Estágio de Pesquisa - Doutorado