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International Journal of Genomics
Volume 2017, Article ID 8737649, 10 pages
https://doi.org/10.1155/2017/8737649
Research Article

Overexpression of Chromosome 21 miRNAs May Affect Mitochondrial Function in the Hearts of Down Syndrome Fetuses

1Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, 80131 Naples, Italy
2Institute of Experimental Endocrinology and Oncology, National Research Council, 80131 Naples, Italy
3Department of Biosciences and Nutrition, Karolinska Institutet, 17177 Stockholm, Sweden

Correspondence should be addressed to Anna Conti; ti.aninu@itnocna

Received 12 May 2017; Revised 20 July 2017; Accepted 2 August 2017; Published 5 September 2017

Academic Editor: Davide Barbagallo

Copyright © 2017 Antonella Izzo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Dosage-dependent upregulation of most of chromosome 21 (Hsa21) genes has been demonstrated in heart tissues of fetuses with Down syndrome (DS). Also miRNAs might play important roles in the cardiac phenotype as they are highly expressed in the heart and regulate cardiac development. Five Hsa21 miRNAs have been well studied in the past: miR-99a-5p, miR-125b-2-5p, let-7c-5p, miR-155-5p, and miR-802-5p but few information is available about their expression in trisomic tissues. In this study, we evaluated the expression of these miRNAs in heart tissues from DS fetuses, showing that miR-99a-5p, miR-155-5p, and let-7c-5p were overexpressed in trisomic hearts. To investigate their role, predicted targets were obtained from different databases and cross-validated using the gene expression profiling dataset we previously generated for fetal hearts. Eighty-five targets of let-7c-5p, 33 of miR-155-5p, and 10 of miR-99a-5p were expressed in fetal heart and downregulated in trisomic hearts. As nuclear encoded mitochondrial genes were found downregulated in trisomic hearts and mitochondrial dysfunction is a hallmark of DS phenotypes, we put special attention to let-7c-5p and miR-155-5p targets downregulated in DS fetal hearts and involved in mitochondrial function. The let-7c-5p predicted target SLC25A4/ANT1 was identified as a possible candidate for both mitochondrial and cardiac anomalies.