title: Valproic acid causes proteasomal degradation of DICER and influences miRNA expression.
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.
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Zhaiyi
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Paolo
authors.initials: P
authors.lastname: Convertini
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Manli
authors.initials: M
authors.lastname: Shen
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Xiu
authors.initials: X
authors.lastname: Xu
authors.affiliation: GenoSplice Technology, Hôpital Saint-Louis, Av Claude Vellefaux, Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lemoine
authors.affiliation: GenoSplice Technology, Hôpital Saint-Louis, Av Claude Vellefaux, Paris, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: de la Grange
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Andres
authors.affiliation: Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky, United States of America.
authors.forename: Stefan
authors.initials: S
authors.lastname: Stamm
mesh_terms: D002478:Cells, Cultured; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D046228:Microarray Analysis; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D059748:Proteolysis / Q000187:drug effects*; D043244:Ribonuclease III / Q000378:metabolism*; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D035683:MicroRNAs; D014635:Valproic Acid; C408087:DICER1 protein, human; D043244:Ribonuclease III; D046988:Proteasome Endopeptidase Complex; D053487:DEAD-box RNA Helicases