Autism spectrum disorder (ASD) includes a heterogeneous group of disorders with different contributing genetics and epigenetics factors. Aberrant expression of miRNAs has been detected in ASD children compared with normally developed children. Due to the heterogeneity of this disorder, there is no consensus on ASD-associated miRNAs; thus, it is necessary to develop a model for comprehensive assessment of the role of miRNAs in ASD. We interrogated the PubMed, Google Scholar, and Web of Science databases until the end of 2019 to identify ASD-associated miRNAs. In addition, mRNA-coding genes that contribute to the pathogenesis of ASD were downloaded from the SFARI GENE (https://gene.sfari.org/). The obtained 201 miRNAs and 478 target mRNAs were imported into the Cytoscape software suite to construct a miRNA-mRNA network. A protein-protein interaction network was constructed for target mRNAs using the CluPedia program in Cytoscape. Using this approach, we detected five modules that were associated with neurexins and neuroligins, glutamatergic synapse, cell adhesion molecules, NOTCH, MECP2 and circadian clock pathways, L1CAM interactions, and neurotransmitter release cycle. Taken together, functional analysis of these genes led to determination of critical pathways related to CNS disorders. Thus, the suggested approach in the current study resulted in the identification of the most relevant pathways in the pathogenesis of ASD that can be used as biomarkers or therapeutic targets.

自闭症谱系障碍 (ASD) 包括一组具有不同贡献遗传学和表观遗传学因素的异质性疾病。与正常发育的儿童相比，已在 ASD 儿童中检测到 miRNA 的异常表达。由于这种疾病的异质性，对 ASD 相关的 miRNA 没有达成共识；因此，有必要开发一个模型来综合评估 miRNA 在 ASD 中的作用。直到 2019 年底，我们查询了 PubMed、Google Scholar 和 Web of Science 数据库，以确定与 ASD 相关的 miRNA。此外，从 SFARI GENE (https://gene.sfari.org/) 下载了有助于 ASD 发病机制的 mRNA 编码基因。将得到的201个miRNA和478个目标mRNA导入Cytoscape软件套件，构建miRNA-mRNA网络。使用 Cytoscape 中的 CluPedia 程序为目标 mRNA 构建了蛋白质-蛋白质相互作用网络。使用这种方法，我们检测到与神经蛋白和神经递质、谷氨酸能突触、细胞粘附分子、NOTCH、MECP2 和生物钟通路、L1CAM 相互作用和神经递质释放周期相关的五个模块。总之，对这些基因的功能分析导致确定与中枢神经系统疾病相关的关键途径。因此，当前研究中建议的方法导致确定了 ASD 发病机制中最相关的途径，可用作生物标志物或治疗靶点。谷氨酸能突触、细胞粘附分子、NOTCH、MECP2 和生物钟通路、L1CAM 相互作用和神经递质释放周期。总之，对这些基因的功能分析导致确定与中枢神经系统疾病相关的关键途径。因此，当前研究中建议的方法导致确定了 ASD 发病机制中最相关的途径，可用作生物标志物或治疗靶点。谷氨酸能突触、细胞粘附分子、NOTCH、MECP2 和生物钟通路、L1CAM 相互作用和神经递质释放周期。总之，对这些基因的功能分析导致确定与中枢神经系统疾病相关的关键途径。因此，当前研究中建议的方法导致确定了 ASD 发病机制中最相关的途径，可用作生物标志物或治疗靶点。