Immunoregulation Unit of the Laboratory of Applied Toxinology (CeTICS/FAPESP), Butantan Institute, São Paulo 05503-900, Brazil.
Int J Mol Sci. 2021 Jul 1;22(13):7117. doi: 10.3390/ijms22137117.
miRNAs regulate gene expression post-transcriptionally in various processes, e.g., immunity, development, and diseases. Since their experimental analysis is complex, in silico target prediction is important for directing investigations. P is a candidate peptide for anti-inflammatory therapy, first discovered in the venom of , which led to miRNAs overexpression in LPS-inflamed zebrafish post-treatment. This work aimed to predict miR-21, miR-122, miR-731, and miR-26 targets using overlapped results of DIANA microT-CDS and TargetScanFish software. This study described 513 miRNAs targets using highly specific thresholds. Using Gene Ontology over-representation analysis, we identified their main roles in regulating gene expression, neurogenesis, DNA-binding, transcription regulation, immune system process, and inflammatory response. miRNAs act in post-transcriptional regulation, but we revealed that their targets are strongly related to expression regulation at the transcriptional level, e.g., transcription factors proteins. A few predicted genes participated concomitantly in many biological processes and molecular functions, such as , , , , , , , , and . Others were particularly involved in innate immunity regulation: , , and . Together, these findings not only provide new insights into the miRNAs mode of action but also raise hope for P therapy and may direct future experimental investigations.
miRNAs 在后转录水平调控各种过程中的基因表达,例如免疫、发育和疾病。由于其实验分析较为复杂,因此计算预测对于指导研究非常重要。P 是一种候选抗炎肽,最初在 的毒液中发现,这导致 LPS 炎症斑马鱼治疗后 miRNA 的过度表达。本研究旨在使用 DIANA microT-CDS 和 TargetScanFish 软件的重叠结果预测 miR-21、miR-122、miR-731 和 miR-26 的靶标。本研究使用高度特异性的阈值描述了 513 个 miRNA 靶标。通过基因本体论过度表达分析,我们确定了它们在调控基因表达、神经发生、DNA 结合、转录调控、免疫系统过程和炎症反应中的主要作用。miRNAs 在后转录水平发挥作用,但我们发现它们的靶标与转录水平的表达调控密切相关,例如转录因子蛋白。少数预测基因同时参与许多生物学过程和分子功能,如、、、、、、、和。其他基因特别参与固有免疫调节:、和。总之,这些发现不仅为 miRNA 的作用模式提供了新的见解,也为 P 治疗带来了希望,并可能指导未来的实验研究。