Integrated microRNA–mRNA Expression Profiling Identifies Novel Targets and Networks Associated with Autism
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 (<i>n</i> = 10) and controls (<i>n</i> = 7...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/12/6/920 |
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| author | Pritmohinder S. Gill Harsh Dweep Shannon Rose Priyankara J. Wickramasinghe Kanan K. Vyas Sandra McCullough Patricia A. Porter-Gill Richard E. Frye |
| author_facet | Pritmohinder S. Gill Harsh Dweep Shannon Rose Priyankara J. Wickramasinghe Kanan K. Vyas Sandra McCullough Patricia A. Porter-Gill Richard E. Frye |
| author_sort | Pritmohinder S. Gill |
| collection | DOAJ |
| description | 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 (<i>n</i> = 10) and controls (<i>n</i> = 7) using RNA and miRNA sequencing profiles. The sequencing analysis identified 1700 genes and 102 miRNAs differentially expressed between the ASD and control LCLs (<i>p</i> ≤ 0.05). The top upregulated genes were <i>GABRA4</i>, <i>AUTS2</i>, and <i>IL27</i>, and the top upregulated miRNAs were <i>hsa-miR-6813-3p</i>, <i>hsa-miR-221-5p</i>, and <i>hsa-miR-21-5p</i>. The RT-qPCR analysis confirmed the sequencing results for randomly selected candidates: <i>AUTS2</i>, <i>FMR1</i>, <i>PTEN, hsa-miR-15a-5p, hsa-miR-92a-3p</i>, and <i>hsa-miR-125b-5p.</i> 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. |
| first_indexed | 2024-03-09T23:20:25Z |
| format | Article |
| id | doaj.art-526b3d6300474987a4558f69c63201cd |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-09T23:20:25Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-526b3d6300474987a4558f69c63201cd2023-11-23T17:27:39ZengMDPI AGJournal of Personalized Medicine2075-44262022-06-0112692010.3390/jpm12060920Integrated microRNA–mRNA Expression Profiling Identifies Novel Targets and Networks Associated with AutismPritmohinder S. Gill0Harsh Dweep1Shannon Rose2Priyankara J. Wickramasinghe3Kanan K. Vyas4Sandra McCullough5Patricia A. Porter-Gill6Richard E. Frye7Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USAThe Wistar Institute, 3601 Spruce St., Philadelphia, PA 19104, USADepartment of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72202, USAThe Wistar Institute, 3601 Spruce St., Philadelphia, PA 19104, USAArkansas Children′s Research Institute, Little Rock, AR 72202, USAArkansas Children′s Research Institute, Little Rock, AR 72202, USAArkansas Children′s Research Institute, Little Rock, AR 72202, USABarrow Neurological Institute at Phoenix Children′s Hospital, Phoenix, AZ 85016, USAAutism 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 (<i>n</i> = 10) and controls (<i>n</i> = 7) using RNA and miRNA sequencing profiles. The sequencing analysis identified 1700 genes and 102 miRNAs differentially expressed between the ASD and control LCLs (<i>p</i> ≤ 0.05). The top upregulated genes were <i>GABRA4</i>, <i>AUTS2</i>, and <i>IL27</i>, and the top upregulated miRNAs were <i>hsa-miR-6813-3p</i>, <i>hsa-miR-221-5p</i>, and <i>hsa-miR-21-5p</i>. The RT-qPCR analysis confirmed the sequencing results for randomly selected candidates: <i>AUTS2</i>, <i>FMR1</i>, <i>PTEN, hsa-miR-15a-5p, hsa-miR-92a-3p</i>, and <i>hsa-miR-125b-5p.</i> 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.https://www.mdpi.com/2075-4426/12/6/920autism spectrum disorderlymphoblastoid cell linesmicroRNAmRNAgene expressionRNA-seq |
| spellingShingle | Pritmohinder S. Gill Harsh Dweep Shannon Rose Priyankara J. Wickramasinghe Kanan K. Vyas Sandra McCullough Patricia A. Porter-Gill Richard E. Frye Integrated microRNA–mRNA Expression Profiling Identifies Novel Targets and Networks Associated with Autism Journal of Personalized Medicine autism spectrum disorder lymphoblastoid cell lines microRNA mRNA gene expression RNA-seq |
| title | Integrated microRNA–mRNA Expression Profiling Identifies Novel Targets and Networks Associated with Autism |
| title_full | Integrated microRNA–mRNA Expression Profiling Identifies Novel Targets and Networks Associated with Autism |
| title_fullStr | Integrated microRNA–mRNA Expression Profiling Identifies Novel Targets and Networks Associated with Autism |
| title_full_unstemmed | Integrated microRNA–mRNA Expression Profiling Identifies Novel Targets and Networks Associated with Autism |
| title_short | Integrated microRNA–mRNA Expression Profiling Identifies Novel Targets and Networks Associated with Autism |
| title_sort | integrated microrna mrna expression profiling identifies novel targets and networks associated with autism |
| topic | autism spectrum disorder lymphoblastoid cell lines microRNA mRNA gene expression RNA-seq |
| url | https://www.mdpi.com/2075-4426/12/6/920 |
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