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GSE61395
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To elucidate the mechanisms by which the mir-200 and the miR-183~96~182 cluster could regulate EMT and thus cellular migration, invasion and metastasis in NSCLC, we searched for common predicted targets of these microRNA families that might have a potential role in these biological processes. First we performed a cross comparison of multiple gene expression datasets from our mouse models of metastasis. We overlapped 224 genes that were elevated greater than four-folds upon Zeb1 induction in 393P cells with 210 genes that showed greater than two-fold increase in expression in the metastatic 344SQ cells compared to the non-metastatic 393P cells and 143 genes that were repressed to less than 0.5-fold in cells with exogenous expression of miR-200. This resulted in an enriched list of 45 genes that are potential miR-200 targets having a role in the process of EMT and metastasis. Next we performed an overlap of genes that were predicted targets of the miR-200 family members and the miR-183~96~182 cluster using the microRNA prediction algorithms miRanda (www.microRNA.org) and identified a list of 17 highly conserved common targets with a mirSVR score less than -6.0. The only 2 genes common in both the overlapping subsets were Zeb1 and Foxf2.
Publication Title
The miR-200 family and the miR-183~96~182 cluster target Foxf2 to inhibit invasion and metastasis in lung cancers.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 R2 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Myb permits multilineage airway epithelial cell differentiation.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 R2 expression beadchip
Description
The epithelium of the pulmonary airway is specially differentiated to provide defense against environmental insults, but also subject to dysregulated differentiation that results in lung disease. The current paradigm for airway epithelial differentiation is a one-step program whereby a p63+ basal epithelial progenitor cell generates a ciliated or secretory cell lineage, but the cue for this transition and whether there are intermediate steps is poorly defined. Here we identify transcription factor Myb as a key regulator that permits early multilineage differentiation of airway epithelial cells. Myb+ cells were identified as p63 and therefore distinct from basal progenitor cells, but were still negative for markers of differentiation.
Publication Title
Myb permits multilineage airway epithelial cell differentiation.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Primary culture airway epithelial cells, grown under physiologic air-liquid interface conditions, with, or without IL-13 in order to study the effects of this cytokine on mucous cell metaplasia, an important feature of asthma and COPD.
Publication Title
IL-13-induced airway mucus production is attenuated by MAPK13 inhibition.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
NextSeq 500
Description
The Iroquois homeodomain transcription factor gene IRX3 is highly expressed in the developing nervous system, limb buds and heart. In adults, expression levels specify risk of obesity. We now report a significant functional role for IRX3 in human acute leukemia. While transcript levels are very low in normal human bone marrow cell populations, high level IRX3 expression is observed in ~30% of patients with acute myeloid leukemia (AML), ~50% of patients with T-acute lymphoblastic leukemia and ~20% of patients with B-acute lymphoblastic leukemia, typically in association with high levels of HOXA9. Expression of IRX3 alone was sufficient to immortalise murine bone marrow stem and progenitor cells, and induce T- and B-lineage leukemias in vivo with incomplete penetrance. IRX3 knockdown induced terminal differentiation of AML cells. Combined IRX3 and Hoxa9 expression in murine bone marrow stem and progenitor cells substantially enhanced the morphologic and phenotypic differentiation block of the resulting AMLs by comparison with Hoxa9-only leukemias, through suppression of a myelomonocytic program. Likewise, in cases of primary human AML, high IRX3 expression is associated with reduced myelomonocytic differentiation. Thus, tissue-inappropriate derepression of IRX3 modulates the cellular consequences of HOX gene expression to enhance differentiation block in human AML. Overall design: Murine acute myeloid leukemias - 3 samples from separate mice with AML initiated by HOXA9 and 3 samples from separate mice with AML initiated by HOXA9 and IRX3 coexpression
Publication Title
Derepression of the Iroquois Homeodomain Transcription Factor Gene IRX3 Confers Differentiation Block in Acute Leukemia.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Zea mays
- 6 Downloadable Samples
- Affymetrix Maize Genome Array (maize)
Description
Plant damage promotes the interaction of lipoxygenases (LOX) with fatty acids yielding 9-hydroperoxides, 13-hydroperoxides and complex arrays of oxylipins. The action of 13-LOX on linolenic acid enables production of 12-oxo-phytodienoic acid (12-OPDA) and its downstream products, termed jasmonates. As signals, jasmonates have related yet distinct roles in the regulation of plant resistance against insect and pathogen attack. A similar pathway involving 9-LOX activity on linolenic and linoleic acid leads to the 12-OPDA positional isomer, 10-oxo-11-phytodienoic acid (10-OPDA) and 10-oxo-11-phytoenoic acid (10-OPEA), respectively; however, physiological roles for 9-LOX cyclopentenones have remained unclear. In developing maize (Zea mays) leaves, southern leaf blight (Cochliobolus heterostrophus) infection results in dying necrotic tissue and the localized accumulation of 10-OPEA, 10-OPDA and a series of related 14- and 12-carbon metabolites, collectively termed death acids. 10-OPEA accumulation becomes wound-inducible within fungal-infected tissues and at physiologically relevant concentrations acts as a phytoalexin by suppressing the growth of fungi and herbivores including Aspergillus flavus, Fusarium verticillioides, and Helicoverpa zea. Unlike previously established maize phytoalexins, 10-OPEA and 10-OPDA display significant phytotoxicity. Both 12-OPDA and 10-OPEA promote the transcription of defense genes encoding glutathione S-transferases, cytochrome P450s, and pathogenesis-related proteins. In contrast, 10-OPEA only weakly promotes the accumulation of multiple protease inhibitor transcripts. Consistent with a role in dying tissue, 10-OPEA application promotes cysteine protease activation and cell death which is inhibited by overexpression of the cysteine protease inhibitor maize cystatin-9. Functions for 10-OPEA and associated death acids are consistent with specialized roles in local defense reactions.
Publication Title
Maize death acids, 9-lipoxygenase-derived cyclopente(a)nones, display activity as cytotoxic phytoalexins and transcriptional mediators.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 23 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
We used microarrays to detail the global program of gene expression underlying rRNA processing gene regulation during heat shock. PBF1 is YBL054W (TOD6) and PBF2 is YER088C (DOT6).
Publication Title
High-resolution DNA-binding specificity analysis of yeast transcription factors.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Analysis of gene expression in lungs of C57BL/6J mice that develop chronic airway disease phenotypes after a single Sendai virus infection, compared with mice treated with UV-inactivated virus.
Publication Title
Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease.
Sample Metadata Fields
Sex, Time
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Mutant KRAS (mut-KRAS) is present in 30% of all human cancers and plays a critical role in cancer cell growth and resistance to therapy. There is evidence from colon cancer that mut-KRAS is a poor prognostic factor and negative predictor of patient response to molecularly targeted therapy. However, evidence for such a relationship in non small cell lung cancer (NSCLC) is conflicting. KRAS mutations are primarily found at codons 12 and 13, where different base changes lead to alternate amino acid substitutions that lock the protein in an active state. The patterns of mut-KRas amino acid substitutions in colon cancer and NSCLC are quite different, with aspartate (D) predominating in colon cancer (50%) and cysteine (C) in NSCLC (47%).
Publication Title
Effect of KRAS oncogene substitutions on protein behavior: implications for signaling and clinical outcome.
Sample Metadata Fields
Sex, Disease, Treatment, Race
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
BRCA1, a well-known breast and ovarian cancer susceptibility gene with multiple interacting partners, is predicted to have diverse biological functions. However, to date its only well-established role is in the repair of damaged DNA and cell cycle regulation. In this regard, the etiopathological study of low penetrant variants of BRCA1 provides an opportunity to uncover its other physiologically important functions. Using this rationale, we studied the R1699Q variant of BRCA1, a potentially moderate risk variant, and found that it does not impair DNA damage repair but abrogates the repression of miR-155, a bona fide oncomir. We further show that in the absence of functional BRCA1, miR-155 is up-regulated in BRCA1-deficient mouse mammary epithelial cells, human and mouse BRCA1-deficienct breast tumor cell lines as well as tumors. Mechanistically, we found that BRCA1 represses miR-155 expression via its association with HDAC2, which deacetylates H2A and H3 on the miR-155 promoter. Finally, we show that over-expression of miR-155 accelerates whereas the knockdown of miR-155 attenuates the growth of tumor cell lines in vivo. Taken together, our findings demonstrate a new mode of tumor suppression by BRCA1 and reveal miR-155 as a potential therapeutic target for BRCA1-deficient tumors.
Publication Title
Tumor suppressor BRCA1 epigenetically controls oncogenic microRNA-155.
Sample Metadata Fields
Specimen part
View Samples