Serum Microrna Profiling in Children with Autism

Friday, May 16, 2014: 11:18 AM
Marquis A (Marriott Marquis Atlanta)
M. M. Vasu1, A. Ayyappan2, I. Thanseem1, K. Suzuki1, M. Tsujii3, T. Sugiyama4 and N. Mori1, (1)Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan, (2)Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan, (3)Department of Contemporary Sociology, Chukyo University, Toyota, Japan, (4)Department of Child and Adolescent Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan
Background: MicroRNAs (miRNAs) are small single-stranded noncoding RNA molecules that are important for brain development and neuronal differentiation. Accumulating evidence suggests usefulness of circulating miRNAs as non-invasive biomarkers for detecting and monitoring various pathophysiological conditions related to neurodevelopment. However, no such microRNA biomarkers in blood samples have yet to be determined for autism.

Objectives:  We assessed the differential expression of neurologically relevant circulating miRNAs in the serum from individuals with autism.

Methods:  Total RNA, including miRNA, was extracted from the serum samples of 55 autistic individuals and 55 age- and gender- 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 autism samples. The differential expression of 14 miRNAs was further validated by SYBR Green quantitative PCR of individual samples. Receiver-operating characteristic analysis was used to evaluate the sensitivity and specificity of miRNAs. The target genes and pathways of miRNAs were predicted using DIANA mirPath.

Results:  Thirteen miRNAs were differentially expressed in autistic 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 a good predictive power to distinguish between control and autism. The target genes of these miRNAs were enriched in several crucial neurological pathways.

Conclusions:  To the best of our knowledge, this is the first study of circulating miRNAs in autism. We have identified a set of serum miRNAs that could be used as non-invasive biomarkers for autism.