Format

Send to

Choose Destination
PLoS One. 2013 Dec 17;8(12):e82895. doi: 10.1371/journal.pone.0082895. eCollection 2013.

Valproic acid causes proteasomal degradation of DICER and influences miRNA expression.

Author information

1
Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky, United States of America.
2
GenoSplice Technology, Hôpital Saint-Louis, Av Claude Vellefaux, Paris, France.

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.

PMID:
24358235
PMCID:
PMC3866160
DOI:
10.1371/journal.pone.0082895
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center