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.
Highlights
As regulators of gene expression, microRNAs play a key role in the transcriptional networks of the developing human brain
Autism spectrum disorder (ASD) refers to a group of heterogeneous neurodevelopmental disorders characterized by impairments in communication and social interaction, and restricted, repetitive and stereotypic patterns of behavior [1]
The differences between the threshold cycle (Ct) values of positive PCR control (PPC) and miRNA reverse transcription control (miRTC) were calculated as
Summary
As regulators of gene expression, microRNAs (miRNAs) play a key role in the transcriptional networks of the developing human brain. 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. Autism spectrum disorder (ASD) refers to a group of heterogeneous neurodevelopmental disorders characterized by impairments in communication and social interaction, and restricted, repetitive and stereotypic patterns of behavior [1]. Owing to the heterogeneous nature of this disorder, classical genetic studies have not necessarily been successful in identifying suitable candidate genes for ASD. In addition to the genetic factors, environmental factors play a vital role in predisposing individuals to ASD [5]. Epigenetic mechanisms, which act at the interface of genes and the environment, have been identified as a potential contributor to the pathogenesis of several neurodevelopmental abnormalities such as ASD [6]. Epigenetic factors control heritable changes in gene expression without changing the DNA sequence [7]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call