title: Atypical miRNA expression in temporal cortex associated with dysregulation of immune, cell cycle, and other pathways in autism spectrum disorders.
abstract: BACKGROUND
  Autism spectrum disorders (ASDs) likely involve dysregulation of multiple genes related to brain function and development. Abnormalities in individual regulatory small non-coding RNA (sncRNA), including microRNA (miRNA), could have profound effects upon multiple functional pathways. We assessed whether a brain region associated with core social impairments in ASD, the superior temporal sulcus (STS), would evidence greater transcriptional dysregulation of sncRNA than adjacent, yet functionally distinct, primary auditory cortex (PAC).
  
  
  METHODS
  We measured sncRNA expression levels in 34 samples of postmortem brain from STS and PAC to find differentially expressed sncRNA in ASD compared with control cases. For differentially expressed miRNA, we further analyzed their predicted mRNA targets and carried out functional over-representation analysis of KEGG pathways to examine their functional significance and to compare our findings to reported alterations in ASD gene expression.
  
  
  RESULTS
  Two mature miRNAs (miR-4753-5p and miR-1) were differentially expressed in ASD relative to control in STS and four (miR-664-3p, miR-4709-3p, miR-4742-3p, and miR-297) in PAC. In both regions, miRNA were functionally related to various nervous system, cell cycle, and canonical signaling pathways, including PI3K-Akt signaling, previously implicated in ASD. Immune pathways were only disrupted in STS. snoRNA and pre-miRNA were also differentially expressed in ASD brain.
  
  
  CONCLUSIONS
  Alterations in sncRNA may underlie dysregulation of molecular pathways implicated in autism. sncRNA transcriptional abnormalities in ASD were apparent in STS and in PAC, a brain region not directly associated with core behavioral impairments. Disruption of miRNA in immune pathways, frequently implicated in ASD, was unique to STS.
authors.affiliation: Department of Neurology, MIND Institute, University of California at Davis Medical Center, 2805 50th Street, Sacramento, CA 95817 USA.
authors.forename: Bradley P
authors.initials: BP
authors.lastname: Ander
authors.affiliation: Department of Psychiatry & Behavioral Sciences, MIND Institute, University of California at Davis Medical Center, 2805 50th Street, Sacramento, CA 95817 USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: Barger
authors.affiliation: Department of Neurology, MIND Institute, University of California at Davis Medical Center, 2805 50th Street, Sacramento, CA 95817 USA.
authors.forename: Boryana
authors.initials: B
authors.lastname: Stamova
authors.affiliation: Department of Neurology, MIND Institute, University of California at Davis Medical Center, 2805 50th Street, Sacramento, CA 95817 USA.
authors.forename: Frank R
authors.initials: FR
authors.lastname: Sharp
authors.affiliation: Department of Psychiatry & Behavioral Sciences, MIND Institute, University of California at Davis Medical Center, 2805 50th Street, Sacramento, CA 95817 USA.
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Schumann
keywords: Auditory cortex; Autism; Superior temporal sulcus; Temporal lobe; miRNA; snoRNA