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Atypical miRNA expression in temporal cortex associated with dysregulation of immune, cell cycle, and other pathways in autism spectrum disorders.

Ander BP, Barger N, Stamova B, Sharp FR, Schumann CM - Mol Autism (2015)

Bottom Line: 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).Immune pathways were only disrupted in STS. snoRNA and pre-miRNA were also differentially expressed in ASD brain.Disruption of miRNA in immune pathways, frequently implicated in ASD, was unique to STS.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, MIND Institute, University of California at Davis Medical Center, 2805 50th Street, Sacramento, CA 95817 USA.

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.

No MeSH data available.


Related in: MedlinePlus

Expression levels of significant miRNA is STS and PAC. Expression levels of microRNA (miRNA) that had significantly increased or decreased expression in ASD compared to control subjects in the superior temporal sulcus and in the primary auditory cortex (P < 0.005 and fold change > /1.2/). ASD values are in red, and control (CTRL) values are in blue. Note that individual subjects are plotted along with box and whisker plots, and the size of the diamonds for each individual corresponds to age of the subject
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Fig3: Expression levels of significant miRNA is STS and PAC. Expression levels of microRNA (miRNA) that had significantly increased or decreased expression in ASD compared to control subjects in the superior temporal sulcus and in the primary auditory cortex (P < 0.005 and fold change > /1.2/). ASD values are in red, and control (CTRL) values are in blue. Note that individual subjects are plotted along with box and whisker plots, and the size of the diamonds for each individual corresponds to age of the subject

Mentions: For the STS, there were 14 sncRNA differentially expressed between ASD and control brains (Table 2). Of the two mature miRNA, miR-4753-5p increased expression and miR-1 decreased expression (Fig. 3, Table 2). For the PAC, there were 16 sncRNA differentially expressed between ASD and control brains (Table 2). Of the four mature miRNA, miR-664-3p and miR-4709-3p increased expression and miR-297 and miR-4742-3p decreased expression (Fig. 3, Table 2).Fig. 3


Atypical miRNA expression in temporal cortex associated with dysregulation of immune, cell cycle, and other pathways in autism spectrum disorders.

Ander BP, Barger N, Stamova B, Sharp FR, Schumann CM - Mol Autism (2015)

Expression levels of significant miRNA is STS and PAC. Expression levels of microRNA (miRNA) that had significantly increased or decreased expression in ASD compared to control subjects in the superior temporal sulcus and in the primary auditory cortex (P < 0.005 and fold change > /1.2/). ASD values are in red, and control (CTRL) values are in blue. Note that individual subjects are plotted along with box and whisker plots, and the size of the diamonds for each individual corresponds to age of the subject
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4491207&req=5

Fig3: Expression levels of significant miRNA is STS and PAC. Expression levels of microRNA (miRNA) that had significantly increased or decreased expression in ASD compared to control subjects in the superior temporal sulcus and in the primary auditory cortex (P < 0.005 and fold change > /1.2/). ASD values are in red, and control (CTRL) values are in blue. Note that individual subjects are plotted along with box and whisker plots, and the size of the diamonds for each individual corresponds to age of the subject
Mentions: For the STS, there were 14 sncRNA differentially expressed between ASD and control brains (Table 2). Of the two mature miRNA, miR-4753-5p increased expression and miR-1 decreased expression (Fig. 3, Table 2). For the PAC, there were 16 sncRNA differentially expressed between ASD and control brains (Table 2). Of the four mature miRNA, miR-664-3p and miR-4709-3p increased expression and miR-297 and miR-4742-3p decreased expression (Fig. 3, Table 2).Fig. 3

Bottom Line: 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).Immune pathways were only disrupted in STS. snoRNA and pre-miRNA were also differentially expressed in ASD brain.Disruption of miRNA in immune pathways, frequently implicated in ASD, was unique to STS.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, MIND Institute, University of California at Davis Medical Center, 2805 50th Street, Sacramento, CA 95817 USA.

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.

No MeSH data available.


Related in: MedlinePlus