title: Serum microRNA profiles in children with autism.
abstract: BACKGROUND
  As 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.
  
  
  METHODS
  Total 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.
  
  
  RESULTS
  Thirteen 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.
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: Department of Psychiatry, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Mundalil Vasu
authors.affiliation: Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Ayyappan
authors.initials: A
authors.lastname: Anitha
authors.affiliation: Department of Psychiatry, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Ismail
authors.initials: I
authors.lastname: Thanseem
authors.affiliation: Department of Psychiatry, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Yamada
authors.affiliation: Department of Psychiatry, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Department of Psychiatry, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Tomoyasu
authors.initials: T
authors.lastname: Wakuda
authors.affiliation: Research Center for Child Mental Development, University of Fukui, 23-3 Matsuokashimoaizuki, Eiheiji, Fukui 910-1193, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Iwata
authors.affiliation: Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan ; Faculty of Sociology, Chukyo University, 101 Tokodachi, Kaizu-cho, Toyota 470-0393, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Tsujii
authors.affiliation: Department of Child and Adolescent Psychiatry, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Toshirou
authors.initials: T
authors.lastname: Sugiyama
authors.affiliation: Department of Psychiatry, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan ; Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, 1-20-1 Handayama, Higashi-ku, Hamamatsu 431-3192, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Mori
keywords: Autism spectrum disorder; complementary DNA; microRNA; microarray; quantitative PCR