Kasimanickam Vanmathy R, Kasimanickam Ramanathan K
Center for Reproductive Biology, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.
Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA 99164, USA.
Animals (Basel). 2023 Apr 30;13(9):1520. doi: 10.3390/ani13091520.
High-throughput in-silico techniques help us understand the role of individual proteins, protein-protein interaction, and their biological functions by corroborating experimental data as epitomized biological networks. The objective of this investigation was to elucidate the association of miRNA-mediated genes in the regulation of dog testes development from immature to adult form by in-silico analysis. Differentially expressed (DE) canine testis miRNAs between healthy immature (2.2 ± 0.13 months; = 4) and mature (11 ± 1.0 months; = 4) dogs were utilized in this investigation. In silico analysis was performed using miRNet, STRING, and ClueGo programs. The determination of mRNA and protein expressions of predicted pivotal genes and their association with miRNA were studied. The results showed protein-protein interaction for the upregulated miRNAs, which revealed 978 enriched biological processes GO terms and 127 KEGG enrichment pathways, and for the down-regulated miRNAs revealed 405 significantly enriched biological processes GO terms and 72 significant KEGG enrichment pathways (False Recovery Rate, < 0.05). The in-silico analysis of DE-miRNA's associated genes revealed their involvement in the governing of several key biological functions (cell cycle, cell proliferation, growth, maturation, survival, and apoptosis) in the testis as they evolve from immature to adult forms, mediated by several key signaling pathways (ErbB, p53, PI3K-Akt, VEGF and JAK-STAT), cytokines and hormones (estrogen, GnRH, relaxin, thyroid hormone, and prolactin). Elucidation of DE-miRNA predicted genes' specific roles, signal transduction pathways, and mechanisms, by mimics and inhibitors, which could perhaps offer diagnostic and therapeutic targets for infertility, cancer, and birth control.
高通量计算机模拟技术通过确证作为典型生物网络的实验数据,帮助我们理解单个蛋白质的作用、蛋白质-蛋白质相互作用及其生物学功能。本研究的目的是通过计算机模拟分析阐明miRNA介导的基因在犬睾丸从幼年到成年发育调控中的关联。本研究使用了健康幼年(2.2±0.13个月;n = 4)和成年(11±1.0个月;n = 4)犬之间差异表达的(DE)犬睾丸miRNA。使用miRNet、STRING和ClueGo程序进行计算机模拟分析。研究了预测的关键基因的mRNA和蛋白质表达及其与miRNA的关联。结果显示,上调的miRNA存在蛋白质-蛋白质相互作用,揭示了978个富集的生物学过程GO术语和127条KEGG富集途径,而下调的miRNA揭示了405个显著富集的生物学过程GO术语和72条显著的KEGG富集途径(错误发现率,q < 0.05)。对DE-miRNA相关基因的计算机模拟分析表明,随着睾丸从幼年发育到成年,它们通过几种关键信号通路(ErbB、p53、PI3K-Akt、VEGF和JAK-STAT)、细胞因子和激素(雌激素、GnRH、松弛素、甲状腺激素和催乳素)介导,参与调控睾丸中的几种关键生物学功能(细胞周期、细胞增殖、生长、成熟、存活和凋亡)。通过模拟物和抑制剂阐明DE-miRNA预测基因的特定作用、信号转导途径和机制,这可能为不孕症、癌症和节育提供诊断和治疗靶点。