Serum microRNA profiles in children with autism

Abstract

BackgroundAs regulators of gene expression, microRNAs (miRNAs) play a key role in the transcriptional networks of the developing human brain. Circulating miRNAs in the serum and plasma are remarkably stable and are suggested to have promise as noninvasive biomarkers for neurological and neurodevelopmental disorders. We examined the serum expression profiles of neurologically relevant miRNAs in autism spectrum disorder (ASD), a complex neurodevelopmental disorder characterized by multiple deficits in communication, social interaction and behavior.MethodsTotal RNA, including miRNA, was extracted from the serum samples of 55 individuals with ASD and 55 age- and sex-matched control subjects, and the mature miRNAs were selectively converted into cDNA. Initially, the expression of 125 mature miRNAs was compared between pooled control and ASD samples. The differential expression of 14 miRNAs was further validated by SYBR Green quantitative PCR of individual samples. Receiver-operating characteristic (ROC) analysis was used to evaluate the sensitivity and specificity of miRNAs. The target genes and pathways of miRNAs were predicted using DIANA mirPath software.ResultsThirteen miRNAs were differentially expressed in ASD individuals compared to the controls. MiR-151a-3p, miR-181b-5p, miR-320a, miR-328, miR-433, miR-489, miR-572, and miR-663a were downregulated, while miR-101-3p, miR-106b-5p, miR-130a-3p, miR-195-5p, and miR-19b-3p were upregulated. Five miRNAs showed good predictive power for distinguishing individuals with ASD. The target genes of these miRNAs were enriched in several crucial neurological pathways.ConclusionsThis is the first study of serum miRNAs in ASD individuals. The results suggest that a set of serum miRNAs might serve as a possible noninvasive biomarker for ASD.

Sexually dimorphic effects of gestational endocrine-disrupting chemicals on microRNA expression in the developing rat hypothalamus

“…Sexual dimorphisms in microRNA expression have become an area of investigation for neurobiological disorders with biases in prevalence and nature, such as autism, schizophrenia, and stroke (70–72). Furthermore, an increase in EDC exposures is beginning to be linked to the rise in these multifactorial disorders (73–75).…”

MicroRNAs in Psychological Stress Reactions and Their Use as Stress-Associated Biomarkers, Especially in Human Saliva

“…Alterations in several circulating miRNA expression levels have been found in psychiatric disorders such as major depressive disorder [64], schizophrenia [65], autism spectrum disorder [66], bipolar disorder [67], Alzheimer disease [68], and mild cognitive impairment [69]. All of these studies describe a possible use of miRNAs as biomarker for the respective disease, mainly in peripheral blood.…”

GLAST But Not Least—Distribution, Function, Genetics and Epigenetics of l-Glutamate Transport in Brain—Focus on GLAST/EAAT1

“…We have found hsa-miR-19b-3p that has been reported to be upregulated in serum of children with autism [67]; in fact, hsa-miR-19b-3p has been suggested as a possible candidate for circulating miRNA-based prediction-marker of autism. Among other miRNA's of interest here, hsa-miR-5585-5p was found to be associated with glioblastoma [68], hsa-miR-5095 and hsa-miR-1273a were detected in microvesicles released from glioma cells [69] and hsa-miR-136-5p was reported as associated with Alzheimer's disease [70].…”