Modular transcriptional repertoire and MicroRNA target analyses characterize genomic dysregulation in the thymus of Down syndrome infants

Autor(es)

Moreira-Filho, Carlos Alberto ^[1] ; Bando, Silvia Yumi ^[1] ; Bertonha, Fernanda Bernardi ^[1] ; Silva, Filipi Nascimento ^[2] ; Costa, Luciano da Fontoura ^[2] ; Ferreira, Leandro Rodrigues ^[1] ; Furlanetto, Glaucio ^[3] ; Chacur, Paulo ^[3] ; Nogueira Zerbini, Maria Claudia ^[4] ; Carneiro-Sampaio, Magda ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med, Dept Pediat, Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Inst Fis Sao Carlos, Sao Carlos, SP - Brazil

^[3] Inst Dante Pazzanese Cardiol, Sao Paulo, SP - Brazil

^[4] Univ Sao Paulo, Fac Med, Dept Patol, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ONCOTARGET; v. 7, n. 7, p. 7497-7533, FEB 16 2016.
• Citações Web of Science: 3

Resumo

Trisomy 21-driven transcriptional alterations in human thymus were characterized through gene coexpression network (GCN) and miRNA-target analyses. We used whole thymic tissue - obtained at heart surgery from Down syndrome (DS) and karyotipically normal subjects (CT) - and a network-based approach for GCN analysis that allows the identification of modular transcriptional repertoires (communities) and the interactions between all the system's constituents through community detection. Changes in the degree of connections observed for hierarchically important hubs/genes in CT and DS networks corresponded to community changes. Distinct communities of highly interconnected genes were topologically identified in these networks. The role of miRNAs in modulating the expression of highly connected genes in CT and DS was revealed through miRNA-target analysis. Trisomy 21 gene dysregulation in thymus may be depicted as the breakdown and altered reorganization of transcriptional modules. Leading networks acting in normal or disease states were identified. CT networks would depict the ``canonical{''} way of thymus functioning. Conversely, DS networks represent a ``non-canonical{''} way, i. e., thymic tissue adaptation under trisomy 21 genomic dysregulation. This adaptation is probably driven by epigenetic mechanisms acting at chromatin level and through the miRNA control of transcriptional programs involving the networks' high-hierarchy genes. (AU)

• Processo FAPESP: 05/00587-5 - Modelagem por redes (grafos) e técnicas de reconhecimento de padrões: estrutura, dinâmica e aplicações
• Beneficiário: Roberto Marcondes Cesar Junior
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/50489-9 - O timo humano: desenvolvimento e doenças
• Beneficiário: Magda Maria Sales Carneiro-Sampaio
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 11/50761-2 - Modelos e métodos de e-Science para ciências da vida e agrárias
• Beneficiário: Roberto Marcondes Cesar Junior
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 08/58238-4 - Autoimunidade na criança: investigação das bases moleculares e celulares da autoimunidade de início precoce
• Beneficiário: Magda Maria Sales Carneiro-Sampaio
• Linha de fomento: Auxílio à Pesquisa - Temático
• Processo FAPESP: 09/53443-1 - Neuroimunologia, genômica funcional e neuroimagem: uma abordagem integrada no estudo da fisiopatologia e tratamento da epilepsia refratária
• Beneficiário: Carlos Alberto Moreira Filho
• Linha de fomento: Auxílio à Pesquisa - Temático