Consiglio, Arianna

Craig, Francesco

Grillo, Giorgio

Licciulli, Flavio

Liuni and Maria Liguori, Sabino

Margari, Lucia

Nuzziello, Nicoletta

Simone, Marta

Attention Deficit Hyperactivity Disorder (ADHD) is a childhood-onset neurodevelopmental
disorder, whose etiology and pathogenesis are still largely unknown. In order to uncover novel
regulatory networks and molecular pathways possibly related to ADHD, we performed an integrated
miRNA and mRNA expression profiling analysis in peripheral blood samples of children with ADHD
and age-matched typically developing (TD) children. The expression levels of 13 miRNAs were
evaluated with microfluidic qPCR, and differentially expressed (DE) mRNAs were detected on an
Illumina HiSeq 2500 genome analyzer. The miRNA targetome was identified using an integrated
approach of validated and predicted interaction data extracted from seven different bioinformatic
tools. Gene Ontology (GO) and pathway enrichment analyses were carried out. Results showed that
six miRNAs (miR-652-3p, miR-942-5p, let-7b-5p, miR-181a-5p, miR-320a, and miR-148b-3p) and 560
genes were significantly DE in children with ADHD compared to TD subjects. After correction for
multiple testing, only three miRNAs (miR-652-3p, miR-148b-3p, and miR-942-5p) remained significant.
Genes known to be associated with ADHD (e.g., B4GALT2, SLC6A9 TLE1, ANK3, TRIO, TAF1, and
SYNE1) were confirmed to be significantly DE in our study. Integrated miRNA and mRNA expression
data identified critical key hubs involved in ADHD. Finally, the GO and pathway enrichment analyses
of all DE genes showed their deep involvement in immune functions, reinforcing the hypothesis
that an immune imbalance might contribute to the ADHD etiology. Despite the relatively small
sample size, in this study we were able to build a complex miRNA-target interaction network in
children with ADHD that might help in deciphering the disease pathogenesis. Validation in larger
samples should be performed in order to possibly suggest novel therapeutic strategies for treating
this complex disease

Nicoletta Nuzziello

Francesco Craig

Marta Simone

Arianna Consiglio

Flavio Licciulli

Lucia Margari

Giorgio Grillo

Sabino Liuni

Maria Liguori

Archivio istituzionale della ricerca - Università di Bari

English

Integrated Analysis of microRNA and mRNA Expression Profiles: An Attempt to Disentangle the Complex Interaction Network in Attention Deficit
Hyperactivity Disorder

Integrated Analysis of microRNA and mRNA

Expression Profiles: An Attempt to Disentangle the

Complex Interaction Network in Attention Deficit

Hyperactivity Disorder

Integrated Analysis of microRNA and mRNA Expression Profiles: An Attempt to Disentangle the Complex Interaction Network in Attention Deficit Hyperactivity Disorder

Abstract

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Archivio istituzionale della ricerca - Università di Bari