Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

14 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ADAR1 regulates the resistance of melanoma cells to T cells via miR-222 and ICAM1

ABSTRACT: The blossom of immunotherapy in melanoma highlights the need to delineate mechanisms of immune resistance. Recently, we have demonstrated that the RNA editing protein, adenosine deaminase acting on RNA-1 (ADAR1) is down-regulated during metastatic transition of melanoma, which enhances melanoma cell proliferation and tumorigenicity. Here we investigate the role of ADAR1 in melanoma immune resistance. Importantly, knockdown of ADAR1 in human melanoma cells induces resistance to tumor infiltrating lymphocytes in a cell contact-dependent mechanism. We show that ADAR1, in an editing-independent manner, regulates the biogenesis of miR-222 at the transcription level and thereby Intercellular Adhesion Molecule 1 (ICAM1) expression, which consequently affects melanoma immune resistance. ADAR1 thus has a novel, pivotal, role in cancer immune resistance. Corroborating with these results, the expression of miR-222 in melanoma tissue specimens was significantly higher in patients who had no clinical benefit from treatment with ipilimumab as compared to patients that responded clinically, suggesting that miR-222 could function as a biomarker for the prediction of response to ipilimumab. These results provide not only novel insights on melanoma immune resistance, but also pave the way to the development of innovative personalized tools to enable optimal drug selection and treatment. 13 formalin fixed paraffin embedded (FFPE) melanoma tissues were stained with hematoxilin and eosin for examination by an expert pathologist. Non-tumor tissue was removed. Total RNA was isolated using miRNeasy FFPE kit (Qiagen) according to the manufacture guidelines.

ORGANISM(S): Homo sapiens

SUBMITTER: jasmine jacob

PROVIDER: E-GEOD-67496 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

ADAR1 regulates the resistance of melanoma cells to T cells via miR-222 and ICAM1

Project description:The blossom of immunotherapy in melanoma highlights the need to delineate mechanisms of immune resistance. Recently, we have demonstrated that the RNA editing protein, adenosine deaminase acting on RNA-1 (ADAR1) is down-regulated during metastatic transition of melanoma, which enhances melanoma cell proliferation and tumorigenicity. Here we investigate the role of ADAR1 in melanoma immune resistance. Importantly, knockdown of ADAR1 in human melanoma cells induces resistance to tumor infiltrating lymphocytes in a cell contact-dependent mechanism. We show that ADAR1, in an editing-independent manner, regulates the biogenesis of miR-222 at the transcription level and thereby Intercellular Adhesion Molecule 1 (ICAM1) expression, which consequently affects melanoma immune resistance. ADAR1 thus has a novel, pivotal, role in cancer immune resistance. Corroborating with these results, the expression of miR-222 in melanoma tissue specimens was significantly higher in patients who had no clinical benefit from treatment with ipilimumab as compared to patients that responded clinically, suggesting that miR-222 could function as a biomarker for the prediction of response to ipilimumab. These results provide not only novel insights on melanoma immune resistance, but also pave the way to the development of innovative personalized tools to enable optimal drug selection and treatment.

2015-12-31 | GSE67496 | GEO

Gene expression over the course of xylem tracheary element formation in cell suspension cultures of Arabidopsis thaliana

Project description:Transcriptomic analysis of gene expression during the differentiation of cell suspension cultures into tracheary elements using the biological system published by Pesquet et al., Current Biology (2010): tracheary element differentiation was triggered by externally supplying hormone-free habituated cell suspension cultures of Arabidopsis thaliana Col-0 with auxin, cytokinin and epibrassinolides; RNA samples extracted from 3 independent time-courses every 12h from 0h to 4 days were analyzed using ATH1 Arabidopsis Affymetrix micro-array Time-course design during tracheary element differentiation (3 independepent time-course were harvested from initiation 0h to 4 days every 12h) - total of 27 samples corresponding to the 3 replicates of 9 time point time-courses - gene expression was monitored along the time-course compared to 0h

2015-09-18 | E-GEOD-73146 | biostudies-arrayexpress

microRNA profiling of lung adenocarcinomas, induced by cRaf overexpression in lung epithelium (Affymetrix)

Project description:In this study we analyzed the expression of miRNAs in the lungs of SP-C/c-raf transgenic mice. The transgene is under the transcriptional control of the surfactant protein C (SP-C) promoter and consists of the oncogenically activated NH2-terminal deletion mutant c-Raf-1-BxB. Overall this study aims at identifying miRNAs regulated in precursor lesions of lung cancer. Affymetrix platform was used to analyze and compare the miRNA expression pattern in RNA extracts derived from two different conditions, i.e. lung of wild type mice and lung of SP-C/c-raf mice expressing the c-Raf-1 transgene. Each gender and condition was tested separately using 6 different individuals from each group: male and female wild type mice (M WT and F WT) and male and female transgenic mice (M c-Raf and F c-Raf).

2013-09-11 | E-GEOD-50748 | biostudies-arrayexpress

Regulation of endometrial bleeding by uNK cells

Project description:Uterine NK cells (uNK) play a role in the regulation of placentation but their functions in non-pregnant endometrium are not understood. We have previously reported suppression of endometrial bleeding and alteration of spiral artery morphology in women exposed to asoprisnil, a progesterone receptor modulator (PRM). We now compare global endometrial gene expression in asoprisnil-treated versus control women and demonstrate a statistically significant reduction of genes in the IL-15 pathway, known to play a key role in uNK development and function. Suppression of IL-15 by asoprisnil was also observed at mRNA level (p<0.05), and immunostaining for NK cell marker CD56 revealed a striking reduction of uNK in asoprisnil-treated endometrium (p<0.001). IL-15 levels in normal endometrium are progesterone-responsive. Progesterone receptor (PR) positive stromal cells transcribe both IL-15 and IL-15RA. Thus, the response of stromal cells to progesterone will be to increase IL-15 trans-presentation to uNK, supporting their expansion and differentiation. In asoprisnil-treated endometrium, there is a marked down-regulation of stromal PR expression and virtual absence of uNK. These novel findings indicate that the IL-15 pathway provides a missing link in the complex interplay between endometrial stromal cells, uNK and spiral arteries affecting physiological and pathological endometrial bleeding. 39 Samples

2013-08-23 | E-GEOD-47577 | biostudies-arrayexpress

Nuclear protein (Nupr)-1 is required for pancreatic adenocarcinoma development in Pdx1-cre;LSL-KrasG12D;Ink4a/Arffl/fl mice

Project description:Nuclear Protein 1 (Nupr1) is a major actor of the cell stress response required for KrasG12D-driven formation of pancreatic intraepithelial neoplastic (PanINs) lesions in mice. We investigated the impact of Nupr1-depletion on the development and biology of murin pancreatic adenocarcinomas (PDAC) in the Pdx1-cre;LSL-KrasG12D;Ink4a/Arffl/fl (KIC) mice. We found that only one half of Nupr1-deficient mice developed PDAC. This is related to increased caspase 3 activity and low IER3 expression in Nupr1-deficient;KIC in the pancreas. Moreover, when Nupr1-deficient;KIC mice do develop PDAC, tumors present with impaired epithelial-to-mesenchymal transition (EMT). Transcriptoma analysis revealed that Nupr1-deficient and Nupr1wt;KIC PDACs presented enrichment of gene signatures of the human classical- and quasi-mesenchymal (QM)-PDAC respectively. Moreover, Nupr1-deficient;KIC PDACs shared with human classical-PDACs overexpression of Kras-activation genes. In addition, cells derived from Nupr1-deficient;KIC PDACs formed fewer microspheres in vitro compared to Nupr1wt;KIC cells, indicative of stemness impairment in the absence of Nupr1. Finally, we found that Nupr1-deficient;KIC cells were more sensitive to some anticancer drugs than their Nupr1wt counterpart. Hence, this study establishes the pivotal role of Nupr1 in PDAC progression after PanIN and in PDAC EMT in vivo, with an impact in PDAC cell stemness. As a consequence, according to absence or presence of Nupr1, KIC mice develop tumors that phenocopy human classical- or QM-PDAC, respectively, thus becoming attractive models for preclinical drug trials. We investigated the impact of the homozygous deletion of the Nupr1 gene on pancreatic adenocarcinoma development and biology in the Pdx1-cre;LSL-KrasG12D;Ink4a/Arffl/fl (KIC) mouse model.

2012-12-16 | E-GEOD-42322 | biostudies-arrayexpress

microRNA profiling of lung adenocarcinomas, induced by cRaf overexpression in lung epithelium

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-09-11 | E-GEOD-50753 | biostudies-arrayexpress

Effect of Lead on Genome-Wide Expression in Developing Mouse Brain during Synaptogenesis

Project description:Lead exposure causes a variety of health effects, especially in children, that may include cognitive and behavioural problems. This study explores the mechanisms associated with this relationship by assessing alterations in gene expression of C57BL/6J pups treated with 50mg/kg lead compared to controls. In addition this study also analyzed brain gene expression differences in Metallothionein I and II (Mt-I and Mt-II) knockout mice treated with lead. Pups of three genotypes (C57BL/6J, Mt-KO with a C57BL/6J background and Heterozygote Mt-KO) were injected with lead acetate during synaptogenesis and weight-matched controls were injected with saline at the same time points. Whole brains were harvested and RNA extracted and pooled from 5 pups and hybridized to Mouse Genome 430 2.0 Arrays. In total 6 arrays were used, one for each genotype and treatment.

2014-01-20 | E-GEOD-26894 | biostudies-arrayexpress

ScRad9-13Myc genome-wide localisation map under galactose induction

Project description:This experiment was performed in order to assess the specificity of Rad9 binding to S. cerevisiae genome. In another ChIP-chip experiment in SC BCS BPS growth conditions we have found Rad9 present to a significant number of genomic loci with a bias to transcriptionally active regions. In order to see if that pattern was random and depended or not on the activity state of the genes, we conducted a Rad9 ChIP on chip experiment with the strain grown in medium with galactose instead of glucose, where it is known that particular gene groups are transcriptionally activated. We then compared to the results of our previous experiment where the strain was grown in glucose.

2014-11-01 | E-MTAB-2201 | biostudies-arrayexpress

Gene expression profiling of Fast vs. Slow Chinese Hamster Ovary cell lines using Wye3aHamster array

Project description:A 3rd generation Wye3aHamster microarray chip was used to carry out a differential expression microarray study of a panel of 30 slow- and fast-growing production cell lines, identifying a priority list of 240 transcripts (110 Up; 130 Down) that passed a statisical filter (ANOVA p-value <0.05, 1.3 fold-change) when the samples were grouped into fast versus slow and pairwise compared and a minimum Pearson Correlation Coefficent (PCC) of >0.7 when growth rate was used as a continuous variable (i.e. included genes have to satisfy BOTH criteria, not just one). This yielded a list of 240 genes. The 240-member genelist yielded 223 Annotated IDs, 203 of which are Unique and all of which are associated with contributing to a high rate of growth in production CHO cell lines. Prospective samples were isolated from 2 distinct groups of clones (slow growers and fast growers), all chosen from the same project (transfection of product transgene into parent line) generated at Pfizer Inc., Bioprocess R&D, Andover, MA, USA. Each group comprised 5 distinct clones, all of which had comparable Qp characteristics. The clones were passaged for 3 or 4 passages over 3-4 days to stabilise the phenotype and freeze stocks. Samples for array hybridization were generated in batch shake flask culture (60ml working volume) with AS1 medium and without feeds or temperature shift. Samples were collected at a single time point (72hrs - mid/late log) and each clone was grown in triplicate flasks, yielding a total of 30 samples for collection and processing. Two bioprocess-relevant variables, viable cell density (VCD) and viability were measured. From the VCD, the growth rate (h-1) was calculated.

2013-01-01 | E-GEOD-37251 | biostudies-arrayexpress

Transcription profiling by array of Arabidopsis thaliana stems to investigate the transcriptome of myb103 mutants to better understand the mechanism underlying MYB103 action

Project description:Two null mutants of MYB103 were found to have decreased expression of FERULATE-5-HYDROXYLASE and reduced syringyl lignin in the basal inflorescence stem. The aim with this microarray experiment was to investigate the transcriptome of these myb103 mutants to better understand the mechanism underlying MYB103 action.

2012-09-01 | E-MEXP-3680 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data