Sustained activation of ERK1/2 by NGF induces microRNA-221 and 222 in PC12 cells

Kazuya Terasawa, Atsuhiko Ichimura, Fumiaki Sato, Kazuharu Shimizu, Gozoh Tsujimoto

Research output: Contribution to journalArticlepeer-review

93 Citations (Scopus)


MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by inhibiting translation and/or inducing degradation of target mRNAs, and they play important roles in a wide variety of biological functions including cell differentiation, tumorigenesis, apoptosis and metabolism. However, there is a paucity of information concerning the regulatory mechanism of miRNA expression. Here we report identification of growth factor-regulated miRNAs using the PC12 cell line, an established model of neuronal growth and differentiation. We found that expression of miR-221 and miR-222 expression were induced by nerve growth factor (NGF) stimulation in PC12 cells, and that this induction was dependent on sustained activation of the extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathway. Using a target prediction program, we also identified a pro-apototic factor, the BH3-only protein Bim, as a potential target of miR-221/222. Overexpression of miR-221 or miR-222 suppressed the activity of a luciferase reporter activity fused to the 3′ UTR of Bim mRNA. Furthermore, overexpression of miR-221/222 decreased endogenous Bim mRNA expression. These results reveal that the ERK signal regulates miR-221/222 expression, and that these miRNAs might contribute to NGF-dependent cell survival in PC12 cells.

Original languageEnglish
Pages (from-to)3269-3276
Number of pages8
JournalFEBS Journal
Issue number12
Publication statusPublished - 2009 Jun


  • Bim
  • ERK1/2
  • MicroRNA
  • NGF
  • PC12

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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