microRNA plays important roles in tumor initiation and progression. Here we showed that, one of the miR-200 family member, miR-141 is drastically under-expressed in several prostate cancer stem cell populations in both xenograft and primary patient samples. Enforced expression of miR-141 in CD44+ PCa cells suppressed tumor initation and metastasis. Cancer stem cell related properties including clonal and sphere formation ability as well as migration and invasion abilites were blocked by miR-141. Moreover, under-expression of miR-141 in prostate cancer stem cells is important in maintaining a partial mesenchymal status. Whole genome sequencing revealed novel pathways that are regulated by miR-141 including Rho GTPase signaling pathway. Stem cell related molecules including CD44 and EZH2 are also validated as direct targets of miR-141 mediating the tumor and metastasis suppressive function. Altogether, these data suggests that on e signal miRNA, miR-141 could utilize multiple mechanisms to obstruct tumor progression and metstasiss. Overall design: Total transcriptome profiles of prostate cancer cells Du145 and LAPC9 transfected with 30nM miR-141 mimicking oligonucleotides or negative control (NC) oligonucleotides were generated by deep sequencing, in duplicates, using Illumina HiSeq 2000.
MicroRNA-141 suppresses prostate cancer stem cells and metastasis by targeting a cohort of pro-metastasis genes.
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View SamplesThe prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here, we describe a whole-genome transcriptome analysis of human benign prostatic basal and luminal populations by using deep RNA sequencing. Combined with comprehensive molecular and biological characterizations, we show that the differential gene expression profiles account for their distinct functional phenotypes. Strikingly, in contrast to luminal cells, basal cells preferentially express gene categories associated with stem cells, neural and neuronal development and RNA processing. Consistent with their expression profiles, basal cells functionally exhibit intrinsic stem-like and proneural properties with enhanced ribosome RNA (rRNA) transcription activity. Of clinical relevance, the treatment failed castration-resistant and anaplastic prostate cancers molecularly resemble a basal-like phenotype. Therefore, we link the cell-type specific gene signatures to subtypes of prostate cancer development, and identify genes associated with patient clinical outcome. Overall design: Human total RNA profiles of 3 pairs of benign prostatic basal and luminal populations freshly purified from prostate tissues of three prostate cancer patients by deep RNA-seq.
Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer.
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View SamplesPurpose: identify sites in endogenous mRNAs that are cut by KSHV SOX; Method: parallel analysis of RNA ends (PARE, following Zhai et al., 2014); Results: SOX cuts at discrete locations in mRNAs Overall design: human Xrn1 was knocked down in HEK293T cells by shRNAs or siRNAs to stabilize degradation fragments with free 5'' ends; GFP-SOX or GFP were transfected for ~24 hrs; total RNA samples were collected and subjected to PARE protocol (Zhai et al., 2014)
Transcriptome-Wide Cleavage Site Mapping on Cellular mRNAs Reveals Features Underlying Sequence-Specific Cleavage by the Viral Ribonuclease SOX.
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View SamplesG9a is an H3K9m2 methyltransferase, which is critical in controlling gene suppression and DNA methylation. We used microarray analysis to identify the target genes that are regulated by G9a in MDA-MB231 cells, in which E-cadherin is silenced.
G9a interacts with Snail and is critical for Snail-mediated E-cadherin repression in human breast cancer.
Specimen part, Cell line, Treatment
View SamplesXEN cells are derived from the primitive endoderm of mouse blastocysts. In culture and in chimeras they exhibit properties of parietal endoderm. However, BMP signaling promotes XEN cells to form an epithelium and differentiate into visceral endoderm (VE). Of the several different subtypes of VE described, BMP induces a subtype that is most similar to the VE adjacent to the trophoblast-derived extraembryonic ectoderm.
BMP signaling induces visceral endoderm differentiation of XEN cells and parietal endoderm.
Treatment
View SamplesEstablishment of a transcriptomic profile of human cells treated with kaemferol, daidzein, kaemferol/genistein, or daidzein/genistein with particular emphasis on signature of genes coding for enzymes involved in glycosaminoglycan synthesis stands for the present study. The hypothesis tested was that kaemferol, daidzein, kaemferol/genistein, and daidzein/genistein influence expression of some genes, among which are those coding for enzymes required for the synthesis of different GAGs being pathologically accumulated in mucopolysaccharidoses. Results provide important information concerning the extent of action of kaemferol, daidzein, kaemferol/genistein, and daidzein/genistein at the molecular level in terms of modulation of gene expression.
Modulation of expression of genes involved in glycosaminoglycan metabolism and lysosome biogenesis by flavonoids.
Specimen part, Cell line, Treatment
View SamplesThe goal of this analysis was to investigate the targets of the influenza A host shutoff ribonuclease PA-X. We profiled the relative levels of cellular RNAs in cells infected with influenza A virus (A/PuertoRico/8/1934 H1N1) comparing wild-type and mutants that make reduced levels of PA-X and/or make a truncated and inactive PA-X. We also profiled relative RNA levels in cells overexpressing wild-type PA-X or a catalytically inactive mutant (D108A). Overall design: for extopic expression, PA-X (from the A/PuertoRico/8/1934 H1N1 (PR8) strain) was expressed in A549 cells using a doxycyline-inducible transgene for 18 hrs; for infection, A549 cells were infected with the wild-type PR8 strain or mutant strain that carried mutations that reduce PA-X production or activity for 15 hrs. rRNA deplete RNA was subjected to high-throughput sequencing
The Influenza A Virus Endoribonuclease PA-X Usurps Host mRNA Processing Machinery to Limit Host Gene Expression.
Treatment, Subject
View SamplesDrought is an important environmental factor affecting plant growth and biomass production. Despite this importance, little is known on the molecular mechanisms regulating plant growth under water limiting conditions. The main goal of this work was to investigate, using a combination of growth and molecular profiling techniques, how Arabidopsis thaliana leaves adapt their growth to prolonged mild osmotic stress. Fully proliferating, expanding and mature leaves were harvested from plants grown on plates without (control) or with 25mM mannitol (osmotic stress) and compared to seedlings at stage 1.03.
Developmental stage specificity and the role of mitochondrial metabolism in the response of Arabidopsis leaves to prolonged mild osmotic stress.
Specimen part
View SamplesXbp1 is a major transcription factor in the unfolded protein response. To uncover its function in DCs we generated a conditional KO for Xbp1 in dendritic cells. We here compare the expression of mRNAs in two different splenic DC subpopulations, CD8a and CD11b DCs in both WT and KO mice.
The unfolded-protein-response sensor IRE-1α regulates the function of CD8α+ dendritic cells.
Specimen part
View SamplesEndocycle is an alternative cell cycle during which the DNA is replicated in the absence of cytokinesis, resulting in cellular endopolyploidy. The endocycle is frequenctly observed in plant species that grow under extreme conditions. Thus, endopolyploidy has been postulated to be a mechanism facilitating adaptive growth.
A Spatiotemporal DNA Endoploidy Map of the Arabidopsis Root Reveals Roles for the Endocycle in Root Development and Stress Adaptation.
Specimen part
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