Differential microRNA editing may drive target pathway switching in human temporal lobe epilepsy
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE211696 | GEO | 2024/01/03
REPOSITORIES: GEO
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Project description:Enforced expression of miRNAs in cells leads to down-regulation of several mRNAs which harbour binding sites in their 3'UTRs for the overexpressed miRNA and represent potential target genes of the miRNA We transfected unedited miR-376a* (376a*A) and edited miR-376a* (376a*G) into SW1783 cells to identify transcripts down-regulated by each in comparison to control miRNA transfection. The aim was to identify target genes subject to direct regulation by miR-376a*A and by miR-376a*G. SW1783 cells (100,000) were transfected with 50 nM of miR-376a*A, miR-376a*G or miR-control. Following incubation for 24 hours, total RNA was isolated from transfected cells. For each (miR-376a*A or miR-376a*G), genes differentially expressed upon miRNA transfection were determined based on comparison with miR-control-transfected samples. Biological triplicates were used for each sample type.
2012-05-31 | E-GEOD-34454 | biostudies-arrayexpress
Project description:Enforced expression of miRNAs in cells leads to down-regulation of several mRNAs, which harbour binding sites in their 3'UTRs for the overexpressed miRNA and represent potential target genes of the miRNA We transfected unedited miR-376a* (376a*A) and edited miR-376a* (376a*G) into U87 cells to identify transcripts down-regulated by each in comparison to control miRNA transfection. The aim was to identify target genes directly subject to regulation by miR-376a*A and by miR-376a*G U87 cells (100,000) were transfected with 50 nM of miR-376a*A, miR-376a*G or miR-control. Following incubation for 24 hours, total RNA was isolated from transfected cells. For each (miR-376a*A or miR-376a*G), genes differentially expressed upon miRNA transfection were determined based on comparison with miR-control-transfected samples. Biological triplicates were used for each sample type.
2012-05-31 | E-GEOD-34455 | biostudies-arrayexpress
Project description:Enforced expression of miRNAs in cells leads to down-regulation of several mRNAs, which harbour binding sites in their 3'UTRs for the overexpressed miRNA and represent potential target genes of the miRNA We transfected unedited miR-376a* (376a*A) and edited miR-376a* (376a*G) into U87 cells to identify transcripts down-regulated by each in comparison to control miRNA transfection. The aim was to identify target genes directly subject to regulation by miR-376a*A and by miR-376a*G
2012-06-01 | GSE34455 | GEO
Project description:Enforced expression of miRNAs in cells leads to down-regulation of several mRNAs which harbour binding sites in their 3'UTRs for the overexpressed miRNA and represent potential target genes of the miRNA We transfected unedited miR-376a* (376a*A) and edited miR-376a* (376a*G) into SW1783 cells to identify transcripts down-regulated by each in comparison to control miRNA transfection. The aim was to identify target genes subject to direct regulation by miR-376a*A and by miR-376a*G.
2012-06-01 | GSE34454 | GEO
Project description:Several biological pathways can be under the regulation of miRNAs. These pathways can be indentified by the enforced expression of a miRNA and analysing the expression data for enrichment of specific pathways represented among the genes differentially expressed upon miRNA overexpression. We transfected unedited miR-376a* (376a*A) and edited miR-376a* (376a*G) into U87 cells to identify differentially regulated transcripts. List of differentially expressed genes were subject to pathway enrichment analysis to identify specific biological processes regulated by each of miR-376a*A and miR-376a*G. U87 cells (100,000) were transfected with 50 nM of miR-376a*A, miR-376a*G or miR-control. Following incubation for 72 hours, total RNA was isolated from transfected cells. For each (miR-376a*A or miR-376a*G), genes differentially expressed upon miRNA transfection were determined based on comparison with miR-control-transfected samples. Biological triplicates were used for each sample type.
2012-05-31 | E-GEOD-34456 | biostudies-arrayexpress
Project description:Several biological pathways can be under the regulation of miRNAs. These pathways can be indentified by the enforced expression of a miRNA and analysing the expression data for enrichment of specific pathways represented among the genes differentially expressed upon miRNA overexpression. We transfected unedited miR-376a* (376a*A) and edited miR-376a* (376a*G) into U87 cells to identify differentially regulated transcripts. List of differentially expressed genes were subject to pathway enrichment analysis to identify specific biological processes regulated by each of miR-376a*A and miR-376a*G.
2012-06-01 | GSE34456 | GEO
Project description:Background: Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disorder, characterized by cardiomyocyte hypertrophy, cardiomyocyte disarray and fibrosis, which has a prevalence of ~1:200-500 and predisposes individuals to sudden death and heart failure. The mechanisms through which diverse HCM-causing mutations cause cardiac dysfunction remain mostly unknown and their identification may reveal new therapeutic avenues. MicroRNAs have emerged as critical regulators of gene expression and disease phenotype in various pathologies. We explored whether miRNAs could play a role in HCM pathogenesis and offer potential therapeutic targets. Methods and Results: Using high-throughput miRNA expression profiling and qPCR analysis in two distinct mouse models of HCM, we found that miR-199a-3p expression levels are upregulated in mutant mice compared to age- and treatment-matched wild-type mice. We also found that miR-199a-3p expression is enriched in cardiac non-myocytes compared to cardiomyocytes. When we expressed miR-199a-3p mimic in cultured primary cardiac non-myocytes and analyzed the conditioned media by proteomics, we found that several ECM proteins (e.g., TSP2, FBLN3, COL11A1, LYOX) were differentially expressed. We confirmed our proteomics findings by qPCR analysis of selected mRNAs and demonstrated that miR-199a-3p mimic expression in cardiac non-myocytes drives upregulation of ECM genes including Tsp2, Fbln3, Pcoc1, Col1a1 and Col3a1. To examine the role of miR-199a-3p in vivo, we inhibited its function using lock-nucleic acid (LNA)-based inhibitors (antimiR-199a-3p) in an HCM mouse model. Our results revealed that progression of cardiac fibrosis is attenuated when miR-199a-3p function is inhibited in mild-to-moderate HCM. Finally, guided by computational target prediction algorithms, we identified mRNAs Cd151 and Itga3 as direct targets of miR-199a-3p and have shown that miR-199a-3p mimic expression negatively regulates AKT activation in cardiac non-myocytes. Conclusions: Altogether, our results suggest that miR-199a-3p may contribute to cardiac fibrosis in HCM through its actions in cardiac non-myocytes. Thus, inhibition of miR-199a-3p in mild-to-moderate HCM may offer therapeutic benefit in combination with complementary approaches that target the primary defect in cardiac myocytes.
2024-01-26 | PXD042904 | Pride
Project description:There are no blood-based molecular biomarkers of temporal lobe epilepsy (TLE) to support clinical diagnosis. MicroRNAs are short noncoding RNAs with strong biomarker potential due to their cell-specific expression, mechanistic links to brain excitability, and stable and reliable detection in biofluids. Altered expression of circulating microRNAs has been reported in human epilepsy, but most studies collected samples from one clinical site, relied on a single platform for profiling or conducted minimal validation. We collected plasma samples from video-electroencephalogram-monitored adult TLE patients at epilepsy specialist centers in two different countries, performed genome-wide PCR-based and RNA sequencing during the discovery phase and validated in a large cohort of samples (>300 samples) that included patients with psychogenic non-epileptic seizures. After profiling, validation of the discovery cohort and validation in the larger patient groups we identified miR-27a-3p, miR-328-3p and miR-654-3p with strong TLE biomarker potential. Plasma levels of these microRNAs were regulated in the same direction in plasma from epileptic mice, and furthermore were not different to healthy controls in patients with psychogenic non-epileptic seizures. The biomarker potential was extended by determining microRNA copy number in plasma and we demonstrate rapid detection of these microRNAs using an electrochemical RNA microfluidic disk as a prototype point-of-care device. Investigation of the molecular transport mechanism in plasma determined analysis of all three microRNAs within the exosome-enriched provided highest diagnostic accuracy while levels of Argonaute-bound miR-328-3p selectively increased in patient samples collected after seizures. In situ hybridization revealed the presence of miR-27a-3p and miR-328-3p within neurons in human brain and bioinformatics analysis predicted targets linked to growth factor signaling and apoptosis. Taken together, this study extends evidence for the biomarker potential of circulating microRNAs for epilepsy diagnosis and mechanistic links to underlying pathomechanisms. microRNA expression in the plasma of 16 patients with TLE, before and after seizure, and 16 controls was measured by TaqMan OpenArray Human MicroRNA Panel.
2019-01-02 | GSE114700 | GEO
Project description:There are no blood-based molecular biomarkers of temporal lobe epilepsy (TLE) to support clinical diagnosis. MicroRNAs are short noncoding RNAs with strong biomarker potential due to their cell-specific expression, mechanistic links to brain excitability, and stable and reliable detection in biofluids. Altered expression of circulating microRNAs has been reported in human epilepsy, but most studies collected samples from one clinical site, relied on a single platform for profiling or conducted minimal validation. We collected plasma samples from video-electroencephalogram-monitored adult TLE patients at epilepsy specialist centers in two different countries, performed genome-wide PCR-based and RNA sequencing during the discovery phase and validated in a large cohort of samples (>300 samples) that included patients with psychogenic non-epileptic seizures. After profiling, validation of the discovery cohort and validation in the larger patient groups we identified miR-27a-3p, miR-328-3p and miR-654-3p with strong TLE biomarker potential. Plasma levels of these microRNAs were regulated in the same direction in plasma from epileptic mice, and furthermore were not different to healthy controls in patients with psychogenic non-epileptic seizures. The biomarker potential was extended by determining microRNA copy number in plasma and we demonstrate rapid detection of these microRNAs using an electrochemical RNA microfluidic disk as a prototype point-of-care device. Investigation of the molecular transport mechanism in plasma determined analysis of all three microRNAs within the exosome-enriched provided highest diagnostic accuracy while levels of Argonaute-bound miR-328-3p selectively increased in patient samples collected after seizures. In situ hybridization revealed the presence of miR-27a-3p and miR-328-3p within neurons in human brain and bioinformatics analysis predicted targets linked to growth factor signaling and apoptosis. Taken together, this study extends evidence for the biomarker potential of circulating microRNAs for epilepsy diagnosis and mechanistic links to underlying pathomechanisms. microRNA expression in the plasma of 16 patients with TLE, before and after seizure, and 16 controls was measured by TaqMan OpenArray Human MicroRNA Panel.
2019-01-02 | GSE114697 | GEO
Project description:Wild-type (WT) miR-378a-3p or edited miR-378a-3p were expressed in SB2 KD-ADAR1 cells to identify the genes regulated by edited miR-378a-3p vs WT miR-378a-3p. PARVA was one of the genes identified to be regulated by edited miR-378a-3p. We demonstrate that this regulation of PARVA is lost in highly metastatic melanoma cells. Microarray analysis was used to evaluate the robustness and reproducibility of the method used to generate the ex vivo tumor tissue model and confirm its ability to recapitulate the essential features of the original tumor.
2018-02-22 | GSE107088 | GEO