MiRNA Cancer Cell Line Profiles
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Alex Adai
PROVIDER: E-GEOD-10833 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:MicroRNAs (miRNAs, miRs) modulate a multitude of cellular events. Here, we identify functional miRNA-protein networks that regulate human monocyte-derived dendritic cell (MDDC) differentiation. MiRNA profiling revealed stage-specific differential expression of 20 miRNAs during days 1, 3 and 5 of MDDC differentiation. To identify and prioritize miRNA-protein networks for functional validation, we developed a target ranking algorithm that incorporates many features of miRNA regulatory networks. This system prioritized miR-21, miR-34a, and their cognate targets WNT1 and JAG1 for functional validation. Inhibition of both miR-21 and miR-34a stalled MDDC differentiation, as quantified by DC-SIGN/CD14 expression ratios, showing cooperative involvement of these miRNAs in MDDC differentiation. We confirmed that the 3â UTRs of WNT1 and JAG1 were functional targets of these miRNAs and provide evidence that these targets were translationally suppressed. Significantly, exogenously added Wnt-1 and Jagged-1 also stalled MDDC differentiation, suggesting that miRNA mediated inhibition of endogenous WNT1 and JAG1 expression was important for proper MDDC differentiation. Finally, inhibition of miR-21 and miR-34a, or addition of Wnt-1 and Jagged-1 led to a decrease in endocytic capacity, a key function of immature DCs. Thus, our novel approach identified and validated some miRNA-protein networks involved in phenotypic and functional MDDC differentiation. monocytes were cultured with GM-CSF and IL-4 for the indicated days (0,1, 3, and 5). Each timepoint was repeated in 3 independent donors (donor 1 , 2, and 3).
2010-06-19 | E-GEOD-15644 | biostudies-arrayexpress
Project description:We aimed to identify miRNA biomarkers of renal injury in kidney biopsies from patients with lupus nephritis. MiRNA profiles of 8 patients were analyzed for correlation with various clinical features including Progression, Activity, Chronicity, and Time to Kidney Failure. MicroRNAs (miRs) are promising biomarkers and are involved in pathogenesis of kidney diseases. We aimed to identify miR biomarkers of renal injury in kidney biopsies from patients with lupus nephritis and study their potential role in renal fibrosis. miR-150 was significantly increased in kidneys with high chronicity compared to low chronicity and it correlated positively with chronicity index scores and renal collagen I expression. In kidneys with high chronicity, miR-150 was found predominantly in proximal tubular cells (PTCs) and was moderately expressed in podocytes and to lesser degree in mesangial cells (MCs). We hypothesized that miR-150 increases fibrosis by downregulating a negative regulator of profibrotic proteins. Suppressor of cytokine signaling1 (SOCS1) is a predicted target of miR-150 and has shown antifibrotic role. After confirming that SOCS1 is a direct target of miR-150, we showed that transfection of a miR-150 analog downregulated SOCS1 protein and upregulated the profibrotic proteins fibronectin, collagen I, collagen III, and TGF-β1 in both primary normal human renal PTCs and MCs. A similar effect was seen when using a SOCS1 siRNA to confirm that the effect of miR-150 on profibrotic proteins is mediated through SOCS1. Stimulation with TGF-β1 induced miR-150 increase in PTCs and human podocytes but not MCs. These results suggest that miR-150 might be a useful quantitative renal biomarker of kidney injury in lupus nephritis and that miR-150, which might be partially induced by TGF-β1, plays an important role in renal fibrosis by increasing profibrotic molecules through downregulation of SOCS1. FFPE kidney specimens (n=25) including baseline and repeated needle renal biopsies were from 14 patients with LN enrolled in IRB-approved protocols at the NIDDK between 1976 and 1999. The specimens were divided in two groups based on histological chronicity index (CI). CI ≥ 4 were categorized as having high degree of chronicity of chronic kidney injury. 18 kidneys from 8 patients including high CI (n=9) and low CI (n=9) were used for miR profiling by Affymetrix microRNA microarrays.
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Project description:SRSF3 is overexpressed in human invasive ovarian cancer and its overexpression is required for cancer cell growth and survival. To decipher the mechnisms behind the role of SRSF3 in ovarian cancer, we examined the gene expression and splicing in the ovarian cancer cell line that was engineered to express a doxycycline-induced SRSF3 siRNA, which was able to knockdown SRSF3 expression by 90% and induce apoptosis. Total RNAs extracted from A2780/SRSF3si2, a subline of ovarian cancer cell line A2780, treated with or without doxycycline at 0.1ug/ml for three days were analyzed using Affymetrix GeneChip® Human Exon 1.0 ST Array
2015-08-06 | E-GEOD-71745 | biostudies-arrayexpress
Project description:Understanding the patterns and processes driving natural genetic variation in gene expression is of fundamental importance to biology. In this study, we examined genetic variation in gene transcription through expression QTL (eQTL) analysis in the Tsu-1 x Kas-1 recombinant inbred line (RIL) mapping population of Arabidopsis thaliana. To understand how natural variation in transcription responds to abiotic stress, we conducted eQTL in both well watered and soil drying conditions. Further, we evaluated whether elements of genome structure were associated with eQTL occurance and genes responding to treatment conditions. Overall, we identified thousands of genes that responded to soil moisture availability and hundreds of eQTLs. However, we identified very few interactions between eQTLs and environmental conditions, and both treatment conditions were enriched for similar gene ontology (GO) categories. We did find strong evidence for associations between genome structure and natural variation in transcription. In general, genes with eQTLs were positively associated with local recombination rates and levels of polymorphism while genes responding to the treatment were negatively correlated with these factors. Our study provides further insight into the origin and maintenance of natural variation in transcription and how that variation responds to environmental conditions. Expression analysis by hybridization to atSNPTILE array (Affymetrix). Seed of the 104 RILs from reciprocal crosses between A. thaliana (L.) Heynh. accessions Kas-1 (CS903) and Tsu-1 (CS1640) were sown on fritted clay (Profile Products LLC, Buffalo Grove, IL) in 2.5-inch pots. Plants were arranged in a randomized complete block design consisting of 4 blocks, and then the pots were refrigerated at 4°C in darkness for 6 d to cold-stratify the seeds prior to commencement of a 12 h photoperiod in Conviron ATC60 growth chambers (Controlled Environments, Winnipeg, MB), at 23°C and 40% humidity during the day and 20°C and 50% humidity during the dark period. Light intensity was approximately 330 µmol m-2 s-1. After four weeks of growth, half of the plants were given a drought treatment, while the others remained fully watered. The drought treatment was randomly assigned to 2 of the 4 blocks and consisted of a slow decrease in soil moisture content over the course of one week. Each day, all pots assigned to the drought treatment were weighed, and water was added to individual pots to bring them to the target gravimetric water content. The target water content decreased each day, in the following series: 100%, 90%, 80%, 70%, 60%, 45%, and 40% of field capacity. At the end of the treatment, leaf tissue was collected from both treatments for RNA extraction.
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