| Autor: |
Gill PS; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA.; Arkansas Children's Research Institute, Little Rock, AR 72202, USA., Dweep H; The Wistar Institute, 3601 Spruce St., Philadelphia, PA 19104, USA., Rose S; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USA.; Arkansas Children's Research Institute, Little Rock, AR 72202, USA., Wickramasinghe PJ; The Wistar Institute, 3601 Spruce St., Philadelphia, PA 19104, USA., Vyas KK; Arkansas Children's Research Institute, Little Rock, AR 72202, USA., McCullough S; Arkansas Children's Research Institute, Little Rock, AR 72202, USA., Porter-Gill PA; Arkansas Children's Research Institute, Little Rock, AR 72202, USA., Frye RE; Barrow Neurological Institute at Phoenix Children's Hospital, Phoenix, AZ 85016, USA.; Department of Child Health, University of Arizona College of Medicine, Phoenix, AZ 85004, USA. |
| Abstrakt: |
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder, with mutations in hundreds of genes contributing to its risk. Herein, we studied lymphoblastoid cell lines (LCLs) from children diagnosed with autistic disorder ( n = 10) and controls ( n = 7) using RNA and miRNA sequencing profiles. The sequencing analysis identified 1700 genes and 102 miRNAs differentially expressed between the ASD and control LCLs ( p ≤ 0.05). The top upregulated genes were GABRA4 , AUTS2 , and IL27 , and the top upregulated miRNAs were hsa-miR-6813-3p , hsa-miR-221-5p , and hsa-miR-21-5p . The RT-qPCR analysis confirmed the sequencing results for randomly selected candidates: AUTS2 , FMR1 , PTEN, hsa-miR-15a-5p, hsa-miR-92a-3p , and hsa-miR-125b-5p. The functional enrichment analysis showed pathways involved in ASD control proliferation of neuronal cells, cell death of immune cells, epilepsy or neurodevelopmental disorders, WNT and PTEN signaling, apoptosis, and cancer. The integration of mRNA and miRNA sequencing profiles by miRWalk2.0 identified correlated changes in miRNAs and their targets' expression. The integration analysis found significantly dysregulated miRNA-gene pairs in ASD. Overall, these findings suggest that mRNA and miRNA expression profiles in ASD are greatly altered in LCLs and reveal numerous miRNA-gene interactions that regulate critical pathways involved in the proliferation of neuronal cells, cell death of immune cells, and neuronal development. |
