Valproic acid causes proteasomal degradation of DICER and influences miRNA expression

Zhaiyi Zhang, Paolo Convertini, Manli Shen, Xiu Xu, Frédéric Lemoine, Pierre De La Grange, Douglas A. Andres, Stefan Stamm

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Valproic acid (VPA) is a commonly used drug to treat epilepsy and bipolar disorders. Known properties of VPA are inhibitions of histone deacetylases and activation of extracellular signal regulated kinases (ERK), which cannot fully explain VPA's clinical features. We found that VPA induces the proteasomal degradation of DICER, a key protein in the generation of micro RNAs. Unexpectedly, the concentration of several micro RNAs increases after VPA treatment, which is caused by the upregulation of their hosting genes prior to DICER degradation. The data suggest that a loss of DICER protein and changes in micro RNA concentration contributes to the clinical properties of VPA. VPA can be used experimentally to down regulate DICER protein levels, which likely reflects a natural regulation of DICER.

Original languageEnglish
Article numbere82895
JournalPLoS ONE
Volume8
Issue number12
DOIs
StatePublished - Dec 17 2013

ASJC Scopus subject areas

  • General

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