摘要
Axon regeneration is crucial for recovery from neurological diseases. Numerous studies have identified several genes, microRNAs (miRNAs), and transcription factors (TFs) that influence axon regeneration. However, the regulatory networks involved have not been fully elucidated. In the present study, we analyzed a regulatory network of 51 miRNAs, 27 TFs, and 59 target genes, which is involved in axon regeneration. We identified 359 pairs of feed- forward loops (FFLs), seven important genes (Naplll, Arhgef12, Sema6d, Akt3, Trim2, Rabllfip2, and Rps6ka3), six important miRNAs (hsa-miR-204-5p, hsa-miR-124-3p, hsa-miR-26a-5p, hsa-miR-16-5p, hsa-miR-17-5p, and hsa- miR-15b-5p), and eight important TFs (Smada2, Flil, Wtl, Sp6, Sp3, Smad4, Smad5, and Crebl), which appear to play an important role in axon regeneration. Functional enrichment analysis revealed that axon-associated genes are involved mainly in the regulation of cellular component organization, axonogenesis, and cell morphogenesis during neuronal differentiation. However, these findings need to be validated by further studies.
创新点:本研究比较详细地阐明了与神经轴突再生相关的微小RNA(mi RNA)、转录因子和靶基因的相互作用关系,为神经系统疾病的恢复奠定基础。方法:本研究从基因表达综合数据库中获得与轴突再生相关的转录因子和基因数据,利用文献报道及生物信息学数据库预测的方法筛选与轴突再生相关的基因靶向mi RNA。利用生物信息学方法分析了三者之间的网络作用关系,预测了在相互作用网络中发挥重要作用的节点。最后对目标基因的基因本体(GO)功能进行了富集。结论:通过分析,初步筛选了与神经轴突再生相关的51个mi RNA、27个转录因子和59个靶标基因。进一步分析得到359对前馈环路,在此基础上推测了神经轴突再生过程中发挥重要作用的7个核心基因(Nap1l1、Arhgef12、Sema6d、Akt3、Trim2、Rab11fip2和Rps6ka3),6个miRNA(hsa-miR-204-5p、hsa-miR-124-3p、hsa-miR-26a-5p、hsamiR-16-5p、hsa-miR-17-5p和hsa-miR-15b-5p)和8个转录因子(Smada2、Fli1、Wt1、Sp6、Sp3、Smad4、Smad5和Creb1)。
基金
Project supported by the Key Project of Hebei North University(No.120177)
the Science and Technology Bureau Research Development Plan of Zhangjiakou City in Hebei(No.0911021D-4)
China