Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Adult mouse liver following benzo(a)pyrene (BaP) treatment: miRNA and mRNa profiling

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Mus musculus

SUBMITTER: Andrew Williams

PROVIDER: E-GEOD-18841 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Lack of change in microRNA expression in adult mouse liver following treatment with benzo(a)pyrene despite robust mRNA transcriptional response.

Yauk Carole Lyn CL Yauk Carole Lyn CL Jackson Kelly K Malowany Morie M Williams Andrew A

Mutation research 20100225 2

Benzo(a)pyrene (BaP) is a mutagenic and carcinogenic environmental contaminant. Metabolic activation of BaP is required for it to exert its mutagenic effects. Metabolism occurs via BaP interaction with the aryl hydrocarbon receptor (AHR) resulting in induction of phase 1 enzymes. Exposure to BaP is expected to cause differential regulation of AHR-responsive genes as well as pathways responding to DNA damage induced by its metabolites. MicroRNAs (miRNAs) are short non-coding molecules that contro ...[more]

PMID: 20188852

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Project description:MicroRNAs (miRNAs) are extensively in diverse biological processes. However, very little is known about the role of miRNAs in mediating thyroid hormones (TH) action. Maintenance of appropriate TH levels is known to be critically important for development, differentiation and maintenance of metabolic balance in mammals. We induced transient hypothyroidism in juvenile mice by short term exposure to methimazole and perchlorate from post natal day (PND) 12 to 15. The expression of miRNAs in the liver was analyzed with the Taqman Low Density Array (containing up to 600 rodent microRNAs). We found the expression of 40 miRNAs was significantly altered in the liver of hypothyroid mice compared to euthyroid controls. Among the miRNAs, miR-1/206/133 exhibited a massive increase in expression (50 – 500 folds). To further explore TH effect on miR-1/206/133, we treated mouse hepatocyte AML 12 cells with 10 nm T3 for 1 hr and 24 hrs. TH treatment induced the down-regulation of miR-1/206/133b at both time points, reaching statistical significance at 24 hrs. To identify the genes targeted by these miRNAs, DNA microarrays were used to examine hepatic mRNA levels in the hypothyroid mouse model alongside controls. We found transcripts from 92 known genes were significantly altered in hypothyroid mice. Web-based target predication softwares (TargetScan and Microcosm) identified 14 of these transcripts as targets of miR-1/106/133. The vast majority of these mRNA targets were significantly down-regulated in hypothyroid mice, corresponding well with the up-regulation of miR-1/206/133 in hypothyroid mouse liver. The results suggest that TH regulation of these genes may occur secondarily via the reduced repression consequent to TH-induced down-regulation of miR-1/206/133. These studies provide novel insight into the role of miRNAs in mediating TH regulation of gene expression. Agilent two-color microarray were used to perform gene expression profile in euthyroid and hypothyroid male mouse livers, 5 biological replicates. TLDA (Taqman microRNA Array) was used to explore the miRNA expression profile in euthyroid and hypothyroid male mouse livers, 4 biological replicates.

Dataset Information

Adult mouse liver following benzo(a)pyrene (BaP) treatment: miRNA and mRNa profiling

Publications

Lack of change in microRNA expression in adult mouse liver following treatment with benzo(a)pyrene despite robust mRNA transcriptional response.

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