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Genome-wide expression profiling after Valproic acid treatment in Saccharomyces cerevisiae

ABSTRACT: Valproic acid (VA) is a small-chain branched fatty acid, widely used as anticonvulsant, and mood stabilizer to treat psychiatric illness. Valproic acid is also known to inhibit the histone deacetylases (HDACs), which makes it as a potent antitumor agent in alone or in combination with other cytotoxic drugs. Beside its conventional activities, valproic acid reported to have much broader, complicated effects and affect many complex physiological processes. However the molecular mechanisms of valproic acid are unclear. So, we used budding yeast transcriptome analysis to better understand the molecular mechanism of action of valproic acid. The clusters of differentially expressed genes in microarray after VA (6mM) treatment and their functional enrichment analysis revealed its overall effects on various biological processes such as cell cycle, signal transduction, metabolism, transcription, ubiquitination, transporter activities and many more. The microarray data were validated by quantitative real-time PCR.

ORGANISM(S): Saccharomyces cerevisiae Schizosaccharomyces pombe

PROVIDER: GSE62400 | GEO | 2016/10/14

SECONDARY ACCESSION(S): PRJNA264015

REPOSITORIES: GEO

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Project description:Congenital malformations are a prevalent cause of infant mortality in the United States and their induction has been linked to a variety of factors, including exposure to teratogens. However, the molecular mechanisms of teratogenicity are not fully understood. MicroRNAs are an important group of small, non-coding RNAs that regulate mRNA expression. MicroRNA roles in early embryonic development are well established, and their disruption during development can cause abnormalities. We hypothesized that developmental exposure to teratogens such as valproic acid alters microRNA expression profiles in developing embryos. Valproic acid is an anticonvulsant and mood-stabilizing drug used to treat epilepsy, bipolar disorder and migraines. To examine the effects of valproic acid on microRNA expression during development, we used zebrafish embryos as a model vertebrate developmental system. Zebrafish embryos were continuously exposed to valproic acid (1 mM) or vehicle control (ethanol) starting from 4 hours post-fertilization (hpf) and sampled at 48 and 96 hpf to determine the miRNA expression profiles prior to and after the onset of developmental defects. At 96 hpf, 95% of the larvae showed skeletal deformities, abnormal swimming behavior, and pericardial effusion. Microarray expression profiling was done using Agilent zebrafish miRNA microarrays. Microarray results revealed changes in miRNA expression at both the time points. Thirteen miRNAs were differentially expressed at 48 hpf and 22 miRNAs were altered at 96 hpf. Among them, six miRNAs (miR-16a, 18c, 122, 132, 457b, and 724) were common to both time points. Bioinformatic target prediction and examination of published literature revealed that these miRNAs target several genes involved in the normal functioning of the central nervous system. These results suggest that the teratogenic effects of valproic acid could involve altered miRNA expression. Small RNA profiles were deteremined in valproic acid exposed zebrafish embryos using Agilent miRNA microarrays

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Genome-wide expression profiling after Valproic acid treatment in Saccharomyces cerevisiae

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