RGD Reference Report - Sustained activation of ERK1/2 by NGF induces microRNA-221 and 222 in PC12 cells. - Rat Genome Database

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

Authors: Terasawa, Kazuya  Ichimura, Atsuhiko  Sato, Fumiaki  Shimizu, Kazuharu  Tsujimoto, Gozoh 
Citation: Terasawa K, etal., FEBS J. 2009 Jun;276(12):3269-76. doi: 10.1111/j.1742-4658.2009.07041.x. Epub 2009 Apr 25.
RGD ID: 152025188
Pubmed: PMID:19438724   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1742-4658.2009.07041.x   (Journal Full-text)

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.




Biological Process

  
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Species
Term
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Evidence
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Original Reference(s)
Mir221Ratcellular response to nerve growth factor stimulus  IEP  RGD 
Mir222Ratcellular response to nerve growth factor stimulus  IEP  RGD 


Genes (Rattus norvegicus)
Mir221  (microRNA 221) Mir222  (microRNA 222)