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. 2021 Feb 16:11:623584.
doi: 10.3389/fgene.2020.623584. eCollection 2020.

Comprehensive circRNA Expression Profile and Construction of circRNAs-Related ceRNA Network in a Mouse Model of Autism

Ji Wang  1   2 , Zhongxiu Yang  3 , Canming Chen  1 , Yang Xu  1 , Hongguang Wang  4 , Bing Liu  5 , Wei Zhang  5 , Yanan Jiang  5   6
Affiliations

Comprehensive circRNA Expression Profile and Construction of circRNAs-Related ceRNA Network in a Mouse Model of Autism

Ji Wang et al. Front Genet. .

Abstract

Autism is a common disease that seriously affects the quality of life. The role of circular RNAs (circRNAs) in autism remains largely unexplored. We aimed to detect the circRNA expression profile and construct a circRNA-based competing endogenous RNA (ceRNA) network in autism. Valproate acid was used to establish an in vivo model of autism in mice. A total of 1,059 differentially expressed circRNAs (477 upregulated and 582 downregulated) in autism group was identified by RNA sequencing. The expression of novel_circ_015779 and novel_circ_035247 were detected by real-time PCR. A ceRNA network based on altered circRNAs was established, with 9,715 nodes and 150,408 edges. Module analysis was conducted followed by GO and KEGG pathway enrichment analysis. The top three modules were all correlated with autism-related pathways involving "TGF-beta signaling pathway," "Notch signaling pathway," "MAPK signaling pathway," "long term depression," "thyroid hormone signaling pathway," etc. The present study reveals a novel circRNA involved mechanisms in the pathogenesis of autism.

Keywords: RNA sequencing (RNA-Seq); autism; ceRNA network; circular RNA (circRNA); in silico analysis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
A mouse model of autism was successfully established. (A) The social interaction test (physical contact). (B) The social interaction test (following). (C) The social interaction test (investigation). (D) Repetitive self-grooming behavior. *P < 0.05 vs. Control; n = 4–5.
Figure 2
Figure 2
Differentially expressed circRNAs in brain from autism mice. (A) Heat map. (B) Volcano plots. (C) The number of differentially expressed circRNAs in a mouse model of autism.
Figure 3
Figure 3
The expression of novel_circ_015779 and novel_circ_035247 in control and autism groups. (A) The expression of novel_circ_015779. (B) The expression of novel_circ_035247. *P < 0.05, **P < 0.01 vs. Control, n = 3.
Figure 4
Figure 4
Top 5 miRNA-related circRNAs-miRNA-mRNA ceRNA network. Circular blue, triangular orange, and square green nodes represent circRNAs, miRNAs, and mRNAs, respectively.
Figure 5
Figure 5
The GO and KEGG pathway enrichment of autism-related circRNAs-miRNA-mRNA ceRNA network. (A) GO enrichment. (B) KEGG pathway enrichment. The color bar represents the q-value.
Figure 6
Figure 6
Module 1 from the autism-related ceRNA network. (A) Module 1 network. (B) GO enrichment. (C) KEGG pathway enrichment. Circular blue, triangular orange, and square green nodes represent circRNAs, miRNAs, and mRNAs, respectively.
Figure 7
Figure 7
Module 2 from the autism-related ceRNA network. (A) Module 2 network. (B) GO enrichment. (C) KEGG pathway enrichment. Circular blue, triangular orange, and square green nodes represent circRNAs, miRNAs, and mRNAs, respectively.
Figure 8
Figure 8
Module 3 from the autism-related ceRNA network. (A) Module 3 network. (B) GO enrichment. (C) KEGG pathway enrichment. Circular blue, triangular orange, and square green nodes represent circRNAs, miRNAs, and mRNAs, respectively.
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