Network analysis of microRNAs, transcription factors, and target genes involved in axon regeneration

J Zhejiang Univ Sci B. 2018;19(4):293-304. doi: 10.1631/jzus.B1700179.

Abstract

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 (Nap1l1, Arhgef12, Sema6d, Akt3, Trim2, Rab11fip2, 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, Fli1, Wt1, Sp6, Sp3, Smad4, Smad5, and Creb1), 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.

Keywords: Transcription factors; miRNAs; Target genes; Axon; Network analysis.

MeSH terms

  • Axons / physiology*
  • Cell Differentiation
  • Cluster Analysis
  • Embryonic Stem Cells / cytology
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Regulatory Networks*
  • Humans
  • MicroRNAs / metabolism*
  • Nerve Regeneration*
  • Neurons / metabolism
  • Software
  • Transcription Factors / metabolism*

Substances

  • MicroRNAs
  • Transcription Factors