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accession-icon SRP014760
TGF-beta/Smad2/3 signaling directly regulates several miRNAs in mouse ES Cells and early embryos
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconIllumina Genome Analyzer II

Description

Purpose: We aimed to identify miRNAs which are induced by the Activin/Nodal effectors, P-Smad2/3, in order to further our understanding of how P-Smad2/3 controls downstream gene expression in mouse ES cells to regulate crucial biological processes. Methods: We used a previously developed Tetracycline-On (Tet-On) system (TAG1) to manipulate the levels of P-Smad2/3 in mouse ES cells and performed an Illumina deep-sequencing screen to identify miRNAs which followed the P-Smad2/3 pathway. Results: We filtered the deep-seq data to identify a list of 28 miRNAs which showed a >1.25 fold increase in response to P-Smad2/3 induction and a >1.25 fold decrease in response to P-Smad2/3 repression. Conclusions: Our study represents a comprehensive global profiling of miRNA expression in response to changes in P-Smad2/3 levels in mouse ES cells. Overall design: miRNA profiles of TAG1 cells which were untreated (control), SB-431541 treated (P-Smad2/3 repressed), or Dox treated (P-Smad2/3 induced), were generated using Illumina GAII.

Publication Title

TGF-β/Smad2/3 signaling directly regulates several miRNAs in mouse ES cells and early embryos.

Sample Metadata Fields

Specimen part, Subject

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accession-icon GSE11865
Downstreams of hnRNP A2 in Colo16 cells
  • organism-icon Homo sapiens
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133A Array (hgu133a)

Description

Limited knowledge of the downstream targets of hnRNP A2/B1 has, however, precluded a clear understanding of their roles in cancer cell growth. To define the pathways in which this protein acts we have now carried out microarray experiments with total RNA from Colo16 epithelial cells transfected with an shRNA that markedly suppresses hnRNP A2/B1 expression. The microarray data identified 123 genes, among 22283 human gene probe sets, with altered expression levels in hnRNP A2/B1-depleted cells. Ontological analysis showed that many of these downstream targets are involved in regulation of the cell cycle and cell proliferation and that this group of proteins is significantly over-represented amongst the affected proteins. The changes detected in the microarray experiments were confirmed by real-time PCR for a subset of proliferation-related genes. Immunoprecipitation-RT-PCR demonstrated that hnRNP A2/B1 formed complexes with the transcripts of many of the verified downstream genes, suggesting that hnRNP A2/B1 contributes to the regulation of these genes.

Publication Title

Downstream targets of heterogeneous nuclear ribonucleoprotein A2 mediate cell proliferation.

Sample Metadata Fields

Sex, Age, Specimen part

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accession-icon GSE40130
Regulation of epidermal growth factor receptor signaling and erlotinib sensitivity in head and neck cancer cells by miR-7
  • organism-icon Homo sapiens
  • sample-icon 10 Downloadable Samples
  • Technology Badge IconIllumina HumanWG-6 v3.0 expression beadchip

Description

Elevated expression and activity of the epidermal growth factor receptor (EGFR)/protein kinase B (Akt) signaling pathway is associated with development, progression and treatment resistance of head and neck cancer (HNC). Several studies have demonstrated that microRNA-7 (miR-7) regulates EGFR expression and Akt activity in a range of cancer cell types via its specific interaction with the EGFR mRNA 3 untranslated region (3-UTR). In the present study, we found that miR-7 regulated EGFR expression and Akt activity in HNC cell lines, and that this was associated with reduced growth in vitro and in vivo of cells (HN5) that were sensitive to the EGFR tyrosine kinase inhibitor (TKI) erlotinib (Tarceva). miR-7 acted synergistically with erlotinib to inhibit growth of erlotinib-resistant FaDu cells, an effect associated with increased inhibition of Akt activity. Microarray analysis of HN5 and FaDu cell lines transfected with miR-7 identified a common set of downregulated miR-7 target genes, providing insight into the tumor suppressor function of miR-7. Furthermore, we identified several target miR-7 mRNAs with a putative role in the sensitization of FaDu cells to erlotinib. Together, these data support the coordinate regulation of Akt signaling by miR-7 in HNC cells and suggest the therapeutic potential of miR-7 alone or in combination with EGFR TKIs in this disease.

Publication Title

Regulation of epidermal growth factor receptor signaling and erlotinib sensitivity in head and neck cancer cells by miR-7.

Sample Metadata Fields

Specimen part, Cell line

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accession-icon SRP171051
Small Sample-Big Data: Integrative Indexed Systems Biology Reveals Dramatic Molecular Ontogeny over the First Week of Human Life in Papua New Guinea
  • organism-icon Homo sapiens
  • sample-icon 50 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

This study examines the global transcriptomic profiles in peripheral blood of Papua New Guinea newborns at birth (D0) comparing with follow up at day 1 (D1), day 3 (D3), or day 7 (D7) post birth. Overall design: Systems biology provides a powerful approach to unravel complex biological processes yet it has not been applied systematically to samples from newborns, a group highly vulnerable to a wide range of diseases. Published methods rely on blood volumes that are not feasible to obtain from newborns. We optimized methods to extract transcriptomic, proteomic, metabolomic, cytokine/chemokine, and single cell immune phenotyping data from <1ml of blood, a volume readily obtained from newborns. Furthermore, indexing to baseline and applying innovative integrative computational methods that address the challenge of few data points with many features enabled identification of robust findings within a readily achievable sample size. This approach uncovered dramatic changes along a stable developmental trajectory over the first week of life. The ability to extract information from 'big data' and draw key insights from such small sample volumes will enable and accelerate characterization of the molecular ontogeny driving this crucial developmental period.

Publication Title

Dynamic molecular changes during the first week of human life follow a robust developmental trajectory.

Sample Metadata Fields

Sex, Subject

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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