Placental Alterations in Autism Spectrum Disorder: An In Silico Approach to circRNA-miRNA-mRNA Networks

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication and repetitive behaviours with an aetiology involving genetic and environmental risk factors. Placental alterations, such as epigenetic DNA methylation and structural abnormalities, have been associated with ASD. Circular RNA (circRNA), covalently closed and highly stable molecules, play an epigenetic role by sequestering microRNA (miRNA) and modulating messenger RNA (mRNA) translation, forming posttranscriptional networks essential for gene expression. However, there is a lack of evidence in the literature regarding the involvement of circRNA, the placenta and ASD. To address this gap, the study aimed to map the interactions among circRNA, miRNA and mRNA, investigating their relevance to ASD and placental development using bioinformatics tools, such as circATLAS and miRTargetLink 2.0. The analysis identified 71 circRNA linked to ASD and 30 highly expressed in the placenta, which regulate pathways such as 'immune response,' 'gene transcription,' and 'replication,' and others previously associated with ASD, such as 'Notch and AKT signalling pathway'. Searches in the SFARI database revealed 11 relevant genes in the ASD group, nine in the placenta group and five shared genes (SRSF11, PSMD11, NOTCH1, CREBBP and TBL1X). Further analysis identified the interaction of the circRNA hsa-MAN1A2_0008 with miRNA associated with these genes. These findings suggest that highly expressed circRNA in the placenta regulate critical pathways for placental development and ASD aetiology, underscoring their role in linking placental alterations to ASD.