Differential microRNA expression profile in blood of children with Down syndrome suggests a role in immunological dysfunction

Autor(es)

Biselli, Joice Matos ; Zampieri, Bruna Lancia ; Matos Biselli-Chicote, Patricia ; Santana de Souza, Jorge Estefano ; Burger, Matheus Carvalho ; da Silva Jr, Wilson Araujo ; Goloni-Bertollo, Eny Maria ; Pavarino, Erika Cristina

• Tipo de documento: Artigo Científico
• Fonte: HUMAN CELL; v. 35, n. 2, p. 10-pg., 2022-01-20.

Resumo

Down syndrome (DS), caused by trisomy of chromosome 21 (HSA21), results in a broad range of phenotypes. However, the determinants contributing to the complex and variable phenotypic expression of DS are still not fully known. Changes in microRNAs (miRNAs), short non-coding RNA molecules that regulate gene expression post-transcriptionally, have been associated with some DS phenotypes. Here, we investigated the genome-wide mature miRNA expression profile in peripheral blood mononuclear cells (PBMCs) of children with DS and controls and identified biological processes and pathways relevant to the DS pathogenesis. The expression of 754 mature miRNAs was profiled in PBMCs from six children with DS and six controls by RT-qPCR using TaqMan(R) Array Human MicroRNA Cards. Functions and signaling pathways analyses were performed using DIANA-miRPath v.3 and DIANA-microT-CDS software. Children with DS presented six differentially expressed miRNAs (DEmiRs): four overexpressed (miR-378a-3p, miR-130b-5p, miR-942-5p, and miR-424-3p) and two downregulated (miR-452-5p and miR-668-3p). HSA21-derived miRNAs investigated were not found to be differentially expressed between the groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed potential target genes involved in biological processes and pathways pertinent to immune response, e.g., toll-like receptors (TLRs) signaling, Hippo, and transforming growth factor beta (TGF-beta) signaling pathways. These results suggest that altered miRNA expression could be contributing to the well-known immunological dysfunction observed in individuals with DS. (AU)

• Processo FAPESP: 10/00153-3 - Expressão de genes envolvidos na resposta imunológica e de micro-RNAs em crianças com síndrome de Down
• Beneficiário: Erika Cristina Pavarino
• Modalidade de apoio: Auxílio à Pesquisa - Regular