Unknown,Transcriptomics,Genomics,Proteomics

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Expression profiling of ncRNAs with custom microarray of lethargic Cacnb4 mutant mice compared to wild type mice

ABSTRACT: For screening mouse models for CNS diseases for changes in ncRNA expression, we first investigated two models with impaired voltage-gated Ca2+ channel activity, i.e. the lethargic mutant of the auxiliary calcium channel β4 subunit (Cacnb4lh; (Burgess et al. 1997)) and knockout mice for the L-type calcium channel CaV1.3 (Platzer et al. 2000), which have been implicated in a variety of neurological disorders such as psychiatric disorders (Cacnb4) or Parkinson’s disease (Cav1.3).

ORGANISM(S): Mus musculus

SUBMITTER: Simon Schafferer

PROVIDER: E-MTAB-2750 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Background: T-cell intracellular antigen (TIA) proteins function as regulators of cell homeostasis. These proteins control gene expression globally at multiple levels in response to dynamic regulatory changes and environmental stresses. Herein we identified a micro(mi)RNA signature associated to transiently TIA-depleted HeLa cells and analyzed the potential role of miRNAs combining genome-wide analysis data on mRNA and miRNA profiles. Results: Using high-throughput miRNA expression profiling, transient depletion of TIA-proteins in HeLa cells was observed to promote significant and reproducible changes (>2-fold, FDR<0.0001) affecting to a pool of up-regulated miRNAs (miR-30b*, miR125a-3p, miR-193a-5p, miR-197_MM2, miR-203, miR-210, miR-371-5p, miR-373*, miR-483-5p, miR-492, miR-498, miR-503, miR-572, miR-586, miR-612, miR-615, miR-623, miR-625, miR-629, miR-638, miR-658, miR-663, miR-671, miR-769-3p and miR-744). Differential expression analysis of some miRNAs was validated by reverse transcription and real time PCR. By target prediction and combined analysis of the genome-wide expression profiles of the mRNAs and miRNAs identified in TIA-depleted HeLa cells, we detected concomitant connections between up-regulated miRNAs and putative and experimental targeted mRNAs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes database analyses suggest that targeted mRNAs are related with biological processes associated to the regulation of DNA-dependent transcription, signal transduction and multicellular organismal development as well as with the enrichment of pathways in cancer, focal adhesion, regulation of actin cytoskeleton and MAPK and Wnt signalling pathways, respectively. Conclusion: All this considered, these observations suggest that specific miRNAs could act as potential mediators of the epigenetic switch linking transcriptomic dynamics and cell phenotypes mediated by TIA proteins. The analysis includes two cell types. Three biological replicates were performed per cell type and they were compared by using three dual-channel microarray hybridizations.

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Expression profiling of ncRNAs with custom microarray of lethargic Cacnb4 mutant mice compared to wild type mice

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