Mir-19 and mir-92 regulate lipid metabolism and energy balance
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Morris Birnbaum
PROVIDER: E-MTAB-2662 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:A subset of breast cancer cells displays increased ability to self-renew and reproduce breast cancer heterogeneity (so called, breast tumour-initiating cells or BT-ICs). As microRNAs (miRNAs) control developmental programs in stem cells, BT-ICs may also rely on specific miRNA profiles for their sustained activity. We analyzed miRNA expression in a model of putative BT-ICs and found that miR-30 family regulates growth under “stemness” conditions. A target screening revealed that miR-30 family modulates the expression of apoptosis and proliferation-related genes. The importance of miR-30 in tumour progression and breast cancer stemness was demonstrated in vivo using a mouse mammary cancer model. This is the first analysis of target prediction in a whole family of microRNAs potentially involved in survival of putative BT-ICs. Total RNA from cells transfected with Pre-miR-30 and KD-miR-30 family and control KD-miR-159 was extracted and reverse-transcribed and hybrized on HT12 Human bead chips
2013-03-22 | E-GEOD-36565 | biostudies-arrayexpress
Project description:Micro RNAs (miRNAs) are a class of small, non-coding RNAs that post-transcriptionally control the translation and stability of mRNAs. In our study, we found a higher level of miR-92a in PMBL versus DLBCL. A bioinformatics approach combining in silico prediction and transcriptomic analyses on patient samples and transduced cell lines, enabled us to identify miR-92a target genes in PMBL.
2016-12-18 | E-MTAB-4165 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are small non-protein-coding RNAs that are incorporated into the RNA-induced silencing complex (RISC) and inhibit gene expression by regulating the stability and/or the translational efficiency of target mRNAs. Previously, we demonstrated that miR-210 is a key player of endothelial cell (EC) response to hypoxia, modulating EC survival, migration and ability to form capillary like-structures. Moreover, the receptor tyrosine kinase ligand Ephrin-A3 was identified as one functionally relevant target. Since each miRNA regulates hundreds of mRNAs, different approaches were combined to identify new miR-210 targets: a Using target prediction software, 32 new miR-210 potential targets were identified. b The proteomic profiling of miR-210 over-expressing ECs identified 11 proteins that were specifically inhibited by miR-210, either directly or indirectly. c Affymetrix based gene expression profiles identified 51 genes that were both down-modulated by miR-210 over-expression and de-repressed when miR-210 was blocked. Surprisingly, only few genes identified either by proteomics or transcriptomics were recognized as miR-210 targets by target prediction algorithms. However, a low-stringency pairing research revealed enrichment for miR-210 putative binding sites, raising the possibility that these genes were targeted via non-canonical recognition sequences. To clarify this issue, miR-210-loaded RISC was purified by immuno-precipitation along with its mRNA targets. The presence of Ephrin-A3 mRNA in the complex validated this approach. We found that 32 potential targets were indeed enriched in miR-210-loaded RISC, and thus can be considered as genuine miR-210 targets. In keeping with this conclusion, we were able to further validate a sub-set of them by 3âUTR-reporter assays. Gene ontology analysis of the targets confirmed the known miR-210 activity in differentiation and cell cycle regulation, highlighting new functions such as involvement in RNA processing, DNA binding, development, membrane trafficking and amino acid catabolism. In conclusion, we validated a multidisciplinary approach for miRNAs target identification and indicated novel molecular mechanisms underpinning miR-210 role in EC response to hypoxia. Experiment Overall Design: Gene expression modifications induced by both miR-210 over-expression and blockade were evaluated. In order to identify new direct and indirect miR-210 targets, transcripts repressed by miR-210 over-expression and up-regulated by miR-210 inhibition (and vice versa) were selected.
2009-11-07 | E-GEOD-16962 | biostudies-arrayexpress
Project description:Heart failure with preserved ejection fraction (HFpEF) remains a major public health burden with increasing prevalence but only few effective therapies. Endothelial dysfunction and inflammation are identified as pathophysiological drivers of HFpEF disease progression. MicroRNAs are increasingly recognized as key regulators of these pathological processes, while antimiR-based therapies have been emerged as promising therapeutics in mice and humans. Therefore, we tested whether targeting miR-92a-3p inhibition is a promising therapeutic intervention to target HFpEF in vivo. By injection of locked nucleic acid (LNA)-based antimiR (LNA-92a) weekly, we demonstrate that inhibition of miR-92a-3p attenuates the development of diastolic dysfunction and left atrial dilation following experimental induction of HFpEF in mice. Indeed, LNA-92a depleted miR-92a-3p expression in the myocardium and peripheral blood, and derepressed predicted target genes in a cell type-specific manner. Furthermore, cell-type specific efficacy of LNA-92a treatment was assessed by single-nuclear RNA sequencing of HFpEF hearts either treated with LNA-92a or LNA-Control. Endothelial cells of LNA-92a treated mice showed normalized vascular gene expression and reduced gene signatures associated with endothelial-mesenchymal transition. Conclusion: This study demonstrates that LNA-based antimiR-92a is an effective therapeutic strategy to target diastolic dysfunction and left atrial dilation in HFpEF.
2024-11-21 | E-MTAB-14589 | biostudies-arrayexpress
Project description:The study of the effects of modification of c-Myb expression on differenatiation of C2C12 cells
2013-10-21 | E-MTAB-1376 | biostudies-arrayexpress
Project description:Defects in stress responses are important contributors in many chronic conditions including cancer, cardiovascular disease, diabetes, and obesity-driven pathologies like non-alcoholic steatohepatitis (NASH). Specifically, endoplasmic reticulum (ER) stress is linked with these pathologies and control of ER stress can ameliorate tissue damage. MicroRNAs have a critical role in regulating diverse stress responses including ER stress. Here we show that miR-494-3p plays a functional role during ER stress. ER stress inducers (tunicamycin and thapsigargin) robustly increase the expression of miR-494 in vitro in an ATF6 dependent manner. Surprisingly, miR-494 pretreatment dampens the induction and magnitude of ER stress in response to tunicamycin in endothelial cells. Conversely, inhibition of miR-494 increases ER stress de novo and amplifies the effects of ER stress inducers. Using Mass Spectrometry (TMT-MS) we identified many proteins that are downregulated by both tunicamycin and miR-494 in cultured human umbilical vein endothelial cells (HUVECs). Among these, we found 6 transcripts which harbor a putative miR-494 binding site. Our data indicates that ER stress driven miR-494 may act in a feedback inhibitory loop to dampen downstream ER stress signaling. We propose that RNA-based approaches targeting miR-494 or its targets may be attractive candidates for inhibiting ER stress dependent pathologies in human disease.
2021-09-09 | PXD019992 | Pride
Project description:MicroRNAs (miRNAs) are small non-protein-coding RNAs that are incorporated into the RNA-induced silencing complex (RISC) and inhibit gene expression by regulating the stability and/or the translational efficiency of target mRNAs. miR-210 can be considered a master miRNA of hypoxic response and is currently regarded as a promising novel non-invasive tumor hypoxia marker. The targets identified to date indicate that miR-210 plays a role in cell cycle regulation, differentiation, mitochondrial metabolism repression, DNA repair and apoptosis. In order to identify miRNAs sub-sequentely modulated by miR-210, miRNA expression profiles of human umbilical vein endothelial cells (HUVEC) over-expressing miR-210 were generated, allowing the identification of miRNAs modulated upon miR-210 up-regulation. HUVEC over-expressing pre-miR-210 or a scramble sequence were generated by retroviral infection, yielding a selected population that expressed mature miR-210 levels comparable with those observed in hypoxic cells. miRNA expression profiles were then measured and miRNAs modulated upon miR-210 up-regulation were identified. This Sample represents four hybridizations - one of which was a dye-swap.
2015-01-01 | E-GEOD-35365 | biostudies-arrayexpress
Project description:miR-101 has been reported as a tumor suppressor in several types of cancer. However, its role in AML is still unknown. In this study, we restored the expression of miR-101 in MLL-AF9 transduced LSK cells by introducing a retroviral miR-101 expression vector. To identify miR-101-regulated gene expression, we performed genome-wide gene expression analysis on GFP+ MLL-AF9-transduced LSK cells overexpressing miR-101 versus control vector. Our gene expression analysis and subsequent functional studies demonstrate that enforced expression of miR-101 has antitumor effects on the development of MLL-rearranged AML. Each group has 3 samples.
2019-07-03 | E-MTAB-7344 | biostudies-arrayexpress
Project description:To identify which miR-148b targets were involved in tumorigenesis, a microarray analysis was performed for miR-148b over-expressing cells versus controls and 129 (49 up and 80 down) modulated genes were revealed. The effects of miR-148b on cancer progression depend on the direct and indirect regulation of multiple target genes. To identify miR-148b modulated genes, MDA-MB-231 cells were transfected with miR-148b precursors or negative controls (pre-miR-148b or control) and used 48h later for microarray and western blot (WB) analyses. When a âWhole Human Genome Oligo Microarrayâ (Agilent) platform was employed, 129 differentially expressed genes (49 upregulated, 80 downmodulated) were found at 48h, considering a fold change (FC) cut of 1.5 and a false discovery rate (FDR) of 16% (Table S4). Crossing these results with the list of putative miR-148b targets (3642) obtained by the miRecords System, we observed that 33 of the modulated genes were also miR-148b predicted targets and interestingly, 26 out of these 33 genes were downmodulated.
2012-12-16 | E-GEOD-26662 | biostudies-arrayexpress
Project description:Colon cancer secretes miR-92a-3p via exosomes. To know the function of miR-92a-3p in extracellular space, we've set endothelial cells (ECs) as a recipient of the exosomes, and examined gene expressions in ECs.
2019-07-01 | E-MTAB-8093 | biostudies-arrayexpress