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. 2022 Mar;35(2):639-648.
doi: 10.1007/s13577-022-00672-x. Epub 2022 Jan 20.

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

Joice Matos Biselli  1 , Bruna Lancia Zampieri  1   2 , Patrícia Matos Biselli-Chicote  1 , Jorge Estefano Santana de Souza  3   4   5 , Matheus Carvalho Bürger  3   5 , Wilson Araújo da Silva Jr  3   5 , Eny Maria Goloni-Bertollo  1 , Érika Cristina Pavarino  6
Affiliations

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

Joice Matos Biselli et al. Hum Cell. 2022 Mar.

Abstract

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® 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 β (TGF-β) signaling pathways. These results suggest that altered miRNA expression could be contributing to the well-known immunological dysfunction observed in individuals with DS.

Keywords: Blood mononuclear cells; Down syndrome; Immune system; Trisomy 21; microRNA expression.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Differentially expressed (DE) microRNAs (miRs) in peripheral blood mononuclear cells (PBMCs) from individuals with Down syndrome (DS) relative to non-DS children (control). The error bars represent the mean ± SEM.*FDR-adjusted P < 0.05
Fig. 2
Fig. 2
Expression patterns of the four chromosome 21 -derived microRNAs detected in peripheral blood mononuclear cells (PBMCs) from individuals with Down syndrome (DS) relative to non-DS children (control). No statistical significance was found (FDR-adjusted P > 0.05). The error bars represent the mean ± SEM
Fig. 3
Fig. 3
Gene Ontology (GO) enrichment analysis of biological processes of the differentially expressed (DE) microRNAs (miRs) targets (DIANA-miRPath v3.0; microT threshold 0.8; P < 0.05; FDR correction; Conservative Stats)
Fig. 4
Fig. 4
Kyoto Encyclopedia of Genes and Genomes (KEGG pathway analysis of target genes of the differentially expressed (DE) microRNAs (miRs) predicted by DIANA-miRPath v3.0 (microT threshold 0.8; P < 0.05; FDR correction; Conservative Stats). The numbers within the figure refer to the number of genes involved in each KEGG pathway
See this image and copyright information in PMC

References

    1. Antonarakis SE, Skotko BG, Rafii MS, et al. Down syndrome. Nat Rev Dis Primers. 2020 doi: 10.1038/s41572-019-0143-7. - DOI - PMC - PubMed
    1. Pavarino Bertelli EC, Biselli JM, Bonfim D, Goloni-Bertollo EM. Clinical profile of children with Down syndrome treated in a genetics outpatient service in the southeast of Brazil. Rev Assoc Med Bras. 2009 doi: 10.1590/S0104-42302009000500017. - DOI - PubMed
    1. Grieco J, Pulsifer M, Seligsohn K, Skotko B, Schwartz A. Down syndrome: cognitive and behavioral functioning across the lifespan. Am J Med Genet C Semin Med Genet. 2015 doi: 10.1002/ajmg.c.31439. - DOI - PubMed
    1. Stoll C, Dott B, Alembik Y, Roth MP. Associated congenital anomalies among cases with Down syndrome. Eur J Med Genet. 2015 doi: 10.1016/j.ejmg.2015.11.003. - DOI - PubMed
    1. Vacca RA, Bawari S, Valenti D, et al. Down syndrome: neurobiological alterations and therapeutic targets. Neurosci Biobehav Rev. 2019 doi: 10.1016/j.neubiorev.2019.01.001. - DOI - PubMed