女性重度抑郁障碍circRNA-miRNA网络相关性及调控机制分析

来源 :中华行为医学与脑科学杂志 | 被引量 : 0次 | 上传用户:delphi_quaker
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目的:基于高通量测序技术获得女性重度抑郁障碍患者外周血差异circRNAs和miRNAs表达谱,进而构建互作网络,再通过功能注释和通路富集分析探索女性抑郁障碍可能存在的发生发展机制。方法:依据ceRNA理论,运用TargetScan软件预测相结合位点,进而构建circRNA-miRNA网络。再对共表达miRNA的靶基因进行预测并进行GO功能富集分析和KEGG通路富集分析,进而筛选出与抑郁障碍相关的关键基因。结果:差异circRNAs共724个;差异miRNAs共26个。hsa_circ_0086092和hsa-miR-146a-3p分别是共表达最高的circRNA和miRNA。GO功能分析显示主要包括含核碱基的化合物代谢过程的调控、RNA剪接的调控、细胞通讯调节、氨基酸转运、RNA代谢过程的调控和信号调节等生物学过程。KEGG通路分析显示靶基因主要富集在神经营养蛋白信号通路、Rap1信号通路、FoxO信号通路、AMPK信号通路、可卡因成瘾、mTOR信号通路、Jak-STAT信号通路、cAMP信号通路等。预测的靶基因中BDNF、FGF2、MAPK14、GRIN2A、GRIN2B、GRM2和PDE4与抑郁障碍相关度最高。结论:hsa_circ_0086092可能通过与hsa-miR-146a-3p的相互作用参与女性重度抑郁障碍的发生发展。“,”Objective:To obtain differential expression profiles of circRNAs and miRNAs in peripheral blood of female patients with major depressive disorder based on high-throughput sequencing technology, and then construct an interaction network.Based on the outcome, it made a further exploration of the possible occurrence and development mechanisms of female major depressive disorder through functional annotation and pathway enrichment analysis.Methods:According to the ceRNA theory, circRNA-miRNA network was constructed by TargetScan software via predicting the binding sites.Subsequently, the GO functional enrichment analysis was performed, and KEGG pathway enrichment analysis were utlized to illustrate the target genes of co-expressed miRNAs.Thereby, the key genes related to major depressive disorder could be screened out.Results:A total of 724 differential circRNAs and 26 differential miRNAs were detected in female patients with major depressive disorder.And hsa_circ_0086092 and hsa-miR-146a-3p were the most co-expressed.Go functional annotations pointed out that it involved the regulation of nucleobase-containing compound metabolic process, regulation of RNA splicing, regulation of cell communication, amino acid transfer, regulation of RNA metabolic process, regulation of signaling and other biological processes.KEGG pathway analysis showed that target genes were mainly enriched in neurotrophin signaling pathway, Rap1 signaling pathway, FoxO signaling pathway, AMPK signaling pathway, cocaine addiction, mTOR signaling pathway, Jak-STAT signaling pathway, cAMP signaling pathway, etcetera.Among the predicted target genes, BDNF, FGF2, MAPK14, GRIN2A, GRIN2B, GRM2 and PDE4 have the highest correlation with major depressive disorder.Conclusion:Hsa_circ_0086092 may be involved in the occurrence and development of female major depressive disorder through interaction with hsa-miR-146a-3p.
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