正文: 既往研究表明miR-181a的上调与癌症密切相关[18],而KEGG信号通路分析亦显示其与小细胞肺癌,前列腺癌,结直肠癌,细胞凋亡,胰腺癌等疾病的发生发展及预后有关,然而其与脑卒中的报道较为新颖,有Moon J M等[19]报道抑制miR-181a可减少神经元损伤,增加Bcl-2蛋白表达表达,并显著抑制谷氨酸转运体。Ouyang Y B等[20]在脑卒中小鼠模型中发现抑制miR-181a,可以减少细胞凋亡,增加细胞存活,保护大脑中风。据KEGG信号通路分析显示,hsa-miR-181a预测靶基因集合显著富集于神经营养因子的信号转导通路。如图2所示,Hsa: 04722信号通路与MAPK,NFκB信号通路密切相关,这些信号通路的紊乱常常与炎症反应及脑卒中的发生发展密切相关,提示miR-181a通过调控靶基因表达参与神经营养因子的信号转导通路,可能是其发挥调控脑卒中作用的分子机制之一。
miRNA对固有免疫受体信号传导的表观遗传调控作用,为各种疾病带来了新的认识。. 但是关于miRNA对TLRs及其它RLRs和NLRs介导的固有免疫反应的调控机制还有待深入。信息学软件的生物学途径及信号通路分析结果,可对miRNAs调控进行有层次的生物学描述,为相应的功能研究提供生物信息学指导,但更确切的结果还需进一步实验验证,且靶基因集合的质量,是直接影响接下来生物富集分析成功与否的最重要的基础之一。本文对TLR4/hsa-miR-181a信号轴的研究,为固有免疫信号通路的调控疾病的研究提供方法,也为miRNAs的功能研究提供新的思路。
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