Expression of MicroRNA-29a Regulated by Yes-Associated Protein Modulates the Neurite Outgrowth in N2a Cells

Biomed Res Int. 2017:2017:5251236. doi: 10.1155/2017/5251236. Epub 2017 Sep 12.

Abstract

Yes-associated protein (YAP) is proved to increase miR-29a in the present study, but the relevant molecular mechanism is not clear. Also, growing evidence indicates that the high-level miR-29a promotes the neurite outgrowth by decreasing PTEN (phosphatase and tensin homologue deleted on chromosome 10). Results show that the expression of miR-29a increases but the PTEN decreases during transfecting the N2a cells with the YAP plasmid. Meanwhile, the advancement of neurite outgrowth is presented via using multiple methods to detect the expression of GAP-43 and NF-200, which have a strong association with neurite outgrowth. The expression of miR-29a, GAP-43, and NF-200 shows an opposite tendency compared to the PTEN when YAP is downregulated. By treating N2a cells with miR-29a mimic and inhibitor, we also find the same conclusion. For in silico analysis of miR-29a, its promoter may have a binding site for YAP. Based on a luciferase reporter assay and a chromatin immunoprecipitation (ChIP) experiment, we demonstrate that YAP could increase the expression of miR-29a by targeting the promoter of miR-29a. In conclusion, the results identify that YAP promotes the neurite outgrowth via targeting the promoter of miR-29a, and it may be an effective therapeutic medicine for the neural disease.

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Axons / metabolism
  • Base Sequence
  • Cell Cycle Proteins
  • Cell Line, Tumor
  • Chromatin Immunoprecipitation
  • Down-Regulation / genetics
  • Gene Expression Regulation, Neoplastic*
  • Genes, Reporter
  • Luciferases / metabolism
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Mutation / genetics
  • Neuronal Outgrowth / genetics*
  • PTEN Phosphohydrolase / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoproteins / metabolism*
  • Promoter Regions, Genetic / genetics
  • Protein Binding / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Up-Regulation / genetics
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • MIRN29 microRNA, mouse
  • MicroRNAs
  • Phosphoproteins
  • YAP-Signaling Proteins
  • Yap1 protein, mouse
  • Luciferases
  • Proto-Oncogene Proteins c-akt
  • PTEN Phosphohydrolase