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Integrative analysis of long noncoding RNAs dysregulation and synapse-associated ceRNA regulatory axes in autism.

Translational psychiatry | 2023

Autism spectrum disorder (ASD) is a complex disorder of neurodevelopment, the function of long noncoding RNA (lncRNA) in ASD remains essentially unknown. In the present study, gene networks were used to explore the ASD disease mechanisms integrating multiple data types (for example, RNA expression, whole-exome sequencing signals, weighted gene co-expression network analysis, and protein-protein interaction) and datasets (five human postmortem datasets). A total of 388 lncRNAs and five co-expression modules were found to be altered in ASD. The downregulated co-expression M4 module was significantly correlated with ASD, enriched with autism susceptibility genes and synaptic signaling. Integrating lncRNAs from the M4 module and microRNA (miRNA) dysregulation data from the literature identified competing endogenous RNA (ceRNA) network. We identified the downregulated mRNAs that interact with miRNAs by the miRTarBase, miRDB, and TargetScan databases. Our analysis reveals that MIR600HG was downregulated in multiple brain tissue datasets and was closely associated with 9 autism-susceptible miRNAs in the ceRNA network. MIR600HG and target mRNAs (EPHA4, MOAP1, MAP3K9, STXBP1, PRKCE, and SCAMP5) were downregulated in the peripheral blood by quantitative reverse transcription polymerase chain reaction analysis (false discovery rate <0.05). Subsequently, we assessed the role of lncRNA dysregulation in altered mRNA levels. Experimental verification showed that some synapse-associated mRNAs were downregulated after the MIR600HG knockdown. BrainSpan project showed that the expression patterns of MIR600HG (primate-specific lncRNA) and synapse-associated mRNA were similar in different human brain regions and at different stages of development. A combination of support vector machine and random forest machine learning algorithms retrieved the marker gene for ASD in the ceRNA network, and the area under the curve of the diagnostic nomogram was 0.851. In conclusion, dysregulation of MIR600HG, a novel specific lncRNA associated with ASD, is responsible for the ASD-associated miRNA-mRNA axes, thereby potentially regulating synaptogenesis.

Pubmed ID: 38057311 RIS Download

Associated grants

  • Agency: National Natural Science Foundation of China (National Science Foundation of China),
    Id: 81971283
  • Agency: National Natural Science Foundation of China (National Science Foundation of China),
    Id: 82271576
  • Agency: National Natural Science Foundation of China (National Science Foundation of China),
    Id: 82171537
  • Agency: National Natural Science Foundation of China (National Science Foundation of China),
    Id: 81671363
  • Agency: National Natural Science Foundation of China (National Science Foundation of China),
    Id: 81730037
  • Agency: National Natural Science Foundation of China (National Science Foundation of China),
    Id: 82071541

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ATCC (tool)

RRID:SCR_001672

Global nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.

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RRID:SCR_005223

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RRID:SCR_008083

Atlas of developing human brain for studying transcriptional mechanisms involved in human brain development. Consists of RNA sequencing and exon microarray data profiling up to sixteen cortical and subcortical structures across full course of human brain development, high resolution neuroanatomical transcriptional profiles of about 300 distinct structures spanning entire brain for four midgestional prenatal specimens, in situ hybridization image data covering selected genes and brain regions in developing and adult human brain, reference atlas in full color with high resolution anatomic reference atlases of prenatal (two stages) and adult human brain along with supporting histology, magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI) data.

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RRID:SCR_017521

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