Baseline assessment of circulating microRNAs near diagnosis of type 1 diabetes predicts future stimulated insulin secretion
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE157177 | GEO | 2020/09/01
REPOSITORIES: GEO
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Project description:Microglia were derived from iPSCs and treated with mimics and inhibitors of the miRNAs hsa-miR-150-5p, hsa-miR-193a-3p and hsa-miR-19b-3p. RNA-sequencing was then performed to examine the effects of up- and down-regulation of the respective miRNAs.
| EGAD00001006842 | EGA
Project description:A considerable proportion of patients with H1-antihistamine-resistant chronic spontaneous urticaria (CSU) fails to respond to omalizumab. However, there is yet no available biomarker that accurately predicts such a response outcome. The utility of blood basophil and eosinophil levels and exosomal and basophil micro(mi)RNAs as biomarkers of response to omalizumab in CSU was explored. In this prospective cohort study of twenty patients with antihistamine-resistant CSU, subjects were treated with 3-monthly doses of omalizumab, and their response assessed using the weekly urticaria activity score (UAS7) for a period of 12-weeks. Basophil and eosinophil levels in the blood and differentially expressed exosomal and basophil miRNAs of complete responders compared to non-responders were identified at baseline. Canonical pathways, altered by differentially expressed miRNAs, were identified using Ingenuity Pathway Analysis (IPA). Complete responders had higher baseline basophil levels (≥21 cells/L) in the peripheral blood compared to non-responders (P = 0.005). Baseline levels of eosinophils did not differ between the study groups. Complete responders in comparison to non-responders had an expression profile characterized by a significantly higher expression of six exosomal miRNAs (miR-6499-5p, miR-7848, miR-4494-3p, miR-450a-2-3p, miR-6877-3p, and miR-3976) and lower expression of miR-141-3p. Complete responders also had higher expression of three basophil miRNAs (miR-1200, miR-1236-3p, and miR-4496). The exosomal miRNA expression profile was predicted by IPA to alter Tec Kinase Signaling pathway activity (P = 0.003).
2021-11-16 | GSE153579 | GEO
Project description:Background: The lack of non-invasive biomarkers imposes the dependence on endoscopy with biopsies for the diagnosis and monitoring of eosinophilic esophagitis (EoE), a prevalent chronic inflammation of the esophagus mediated by a type 2 immune response. We aimed to identify potential non-invasive biomarkers using microRNAs (miRNAs) in plasma-derived extracellular vesicles (pEVs). Methods: This is a prospective single-center observational study including a discovery cohort of EoE patients (n=26) with active disease (EoE.Basal) and after anti-inflammatory treatment (EoE.Post.tx), and control subjects (n=16). Small-RNA-seq of RNA-pEVs was performed to identify differentially regulated small-RNAs (sRNAs) in EoE.Basal vs. controls and EoE.Basal vs. EoE.Post.tx comparisons. Candidate miRNAs were validated in an independent cohort (EoE patients, n=33; controls, n=14), and the diagnostic potential of miRNAs-pairs was assessed. Results: the pEVs-sRNA cargo differed among controls, EoE.Basal and EoE.Post.tx conditions. Compared with controls, Ser_Comb_22, Leu_Comb_5, miR-10b-5p and miR-125a-5 were upregulated in EoE.Basal, and miR-224-5p, miR-221-3p, let-7d-5p and miR-191-5p were downregulated. Combination of miR-221-3p and miR-10b-5p showed the best diagnostic performance in discovery (AUC=0.87) and validation (AUC=0.70) cohorts. Comparing EoE.Basal and EoE.Post.tx paired samples, miR-374a-5p and miR-30a-3p were upregulated in EoE.Basal, while miR-15a-5p and let-7d-5p were downregulated. Here, combination of mi-30a-3p and miR-15a-5p showed AUC values of 0.90 and 0.71 in discovery and validation cohorts respectively. MiR-30a-3p remained highly upregulated in EoE.Basal when compared to EoE.Post.tx in the validation cohort (p=0.001). Conclusions: The sRNA cargo of pEVs is related to the inflammatory activity in EoE. This study pioneers the use of pEVs as a non-invasive biomarker for EoE.
2024-10-15 | GSE275710 | GEO
Project description:WNT signaling is fundamental to bone health and its aberrant activation leads to skeletal pathologies. A heterozygous missense mutation p.C218G in WNT1, a key WNT pathway ligand, leads to severe early-onset osteoporosis with multiple peripheral and spinal fractures. Despite the severe skeletal manifestations, conventional bone markers are normal in mutation-positive patients. The objective of this study was to find novel biomarkers that differentiate between WNT1 mutation-positive and -negative subjects. We evaluated serum levels of 192 miRNAs in 12 mutation-positive (median age 39 years, range 11-76 years) and 12 mutation-negative (35 years, range 9-59 years) subjects from two Finnish families. The results indicate significant differences in circulating miRNA profiles with 2 upregulated (miR-18a-3p, miR-223-3p) and 6 downregulated miRNAs (miR-22-3p, miR-31-5p, miR-34a-5p, miR-143-5p miR-423-5p, miR 423-3p) in the mutation-positive subjects. Three of these (miR-22-3p, miR-34a-5p, and miR-31-5p) are known inhibitors of WNT signaling: miR-22-3p and miR-34a-5p target WNT1 mRNA and miR-31-5p is predicted to bind to the WNT1 3’UTR. Our results suggest that the WNT1 mutation disrupts a feed-back regulation between these miRNAs and WNT1, providing new insights into the pathogenesis of WNT-related bone disorders. Future studies are warranted to explore the potential diagnostic and therapeutic applications of these findings in osteoporosis.
2018-03-29 | GSE103473 | GEO
Project description:Rationale: Currently, there are no blood-based biomarkers with clinical utility for acute ischemic stroke (IS). microRNAs (miRNAs) show promise as disease markers due to their cell-type specific expression patterns and stability in peripheral blood. Objective: To identify circulating miRNAs associated with acute IS, determine their temporal course up to 90 days post-stroke, and explore their utility as an early diagnostic marker. Methods and Results: We used RNA sequencing to study expression changes of circulating miRNAs in a discovery sample of 20 IS patients and 20 matched healthy control subjects (HCs). We further applied qRT-PCR in independent samples for validation (40 IS patients and 40 matched controls), replication (200 IS patients, 100 HCs), and in 72 patients with transient ischemic attacks (TIA). Sampling of patient plasma was done immediately upon hospital arrival. We identified, validated, and replicated three differentially expressed miRNAs, which were upregulated in IS patients compared to both HCs (miR-125a-5p [1.8-fold; P=1.5x10-6], miR-125b-5p [2.5-fold; P=5.6x10-6], and miR-143-3p [4.8-fold; P=7.8x10-9]) and TIA patients (miR-125a-5p: P=0.003, miR-125b-5p: P=0.003, miR-143-3p: P=0.005). Longitudinal analysis of expression levels up to 90 days after stroke revealed a normalization to control levels for miR-125b-5p and miR-143-3p starting at day two, while miR-125a-5p remained elevated. Levels of all three miRNAs depended on platelet numbers in a platelet spike-in experiment, but were unaffected by chemical hypoxia in N2a cells and in experimental stroke models. In a random forest classification, miR-125a-5p, miR-125b-5p and miR-143-3p differentiated between HCs and IS patients with an area under the curve (AUC) of 0.90 (sensitivity: 85.6%; specificity: 76.3%), which was superior to multimodal cranial computed tomography obtained for routine diagnostics (sensitivity: 72.5%) and previously reported biomarkers of acute IS (neuron specific enolase: AUC=0.69, interleukin 6: AUC=0.82). Conclusions: A set of circulating miRNAs (miR-125a-5p, miR-125b-5p, miR-143-3p) associates with acute IS and might have clinical utility as an early diagnostic marker.
2018-02-22 | GSE110993 | GEO
Project description:MiRNAs regulate posttranscriptional gene expression and are widely implicated in the pathogenesis of complex diseases. We aim to elucidate miRNA regulation of the atrial mRNA signatures that associate with AF. This may provide novel mechanistical insights and candidate targets for therapies using miRNA mimics or antimiRs.
We present combined miRNAs-mRNAs sequencing in atrial tissues of patient without AF (n=22), with paroxysmal AF (n=22) and with persistent AF (n=20). MiRNA and mRNA signatures followed an ordinal scale from nonAF to paroxysmal to persistent AF patients. The previously reported mRNA sequencing identified 5228 differentially expressed genes involved in epithelial to mesenchymal transition, endothelial cell proliferation and extracellular matrix remodelling involving collagens, glycoproteins and proteoglycans. We discovered 103 differentially expressed miRNAs. Key downregulated miRNAs included miR-135b-5p, miR-138-5p, miR-200a-3p, miR-200b-3p and miR-31-5p and key upregulated miRNAs were miR-144-3p, miR-15b-3p, miR-182-5p miR-18b-5p, miR-4306 and miR-206. The expression levels of differentially expressed miRNAs were negatively correlated with the expression levels of their predicted target mRNAs. The downregulated miRNAs demonstrated a more profound transcriptome effect than the upregulated miRNAs. Upregulated biological processes enriched in miRNAs targets related to epithelial and endothelial cell migration and glycosaminoglycan biosynthesis, in line with the processes discovered by the mRNA sequencing analysis.
Combined analysis of miRNA and mRNA sequencing uncovered miRNAs with a broad transcriptional effect in human AF. Epithelial to mesenchymal transition and endothelial cell proliferation were processes controlled by downregulated miR-135b-5p, miR-138-5p, miR-200a-3p, miR-200b-3p and miR-31-5p, which in turn may contribute to (myo)fibroblast activation and structural remodeling.\
| EGAS00001005296 | EGA
Project description:iPSC-derived neurons were treated with mimics and inhibitors of the miRNAs miR-150-5p, hsa-mir-193a-3p and hsa-miR-19b-3p.
RNA-sequencing was then performed to examine the effects of miRNA up-regulation and inhibition.
| EGAD00001006844 | EGA
Project description:We tested the hypothesis that a panel of placental mammal-specific miRNAs and their targets play important to establish receptivity to implantation and their dysregulated expression may be a feature in women with early pregnancy loss. Relative expression levels of miR-340-5p, −542-3p, and −671-5p all increased following treatment of Ishikawa cells with progesterone (10 μg/ml) for 24 hrs (p < 0.05). RNA sequencing of these P4-treated cells identified co-ordinate changes to 6,367 transcripts of which 1713 were predicted targets of miR-340-5p, 670 of miR-542-3p, and 618 of miR-671-5p. Quantitative proteomic analysis of Ishikawa cells transfected with mimic or inhibitor (48 hrs: n=3 biological replicates) for each of the P4-regulated miRNAs was carried out to identify targets of these miRNAs. Excluding off target effects, mir-340-5p mimic altered 1,369 proteins while inhibition changed expression of 376 proteins (p < 0.05) of which, 72 were common to both treatments. A total of 280 proteins were identified between predicted (mirDB) and confirmed (in vitro) targets. In total, 171 proteins predicted to be targets by mirDB were altered in vitro by treatment with miR-340-5p mimic or inhibitor and were also altered by treatment of endometrial epithelial cells with P4. In vitro targets of miR-542-3p identified 1,378 proteins altered by mimic while inhibition altered 975 a core of 200 proteins were changed by both. 100 protein targets were predicted and only 46 proteins were P4 regulated. miR-671-mimic altered 1,252 proteins with inhibition changing 492 proteins of which 97 were common to both, 95 were miDB predicted targets and 46 were also P4-regulated. All miRNAs were detected in endometrial biopsies taken from patients during the luteal phase of their cycle, irrespective of prior or future pregnancy outcomes Expression of mir-340-5p showed an overall increase in patients who had previously suffered a miscarriage and had a subsequent miscarriage, as compared to those who had infertility or previous miscarriage and subsequently went on to have a life birth outcome. The regulation of these miRNAs and their protein targets regulate the function of transport and secretion, and adhesion of the endometrial epithelia required for successful implantation in humans. Dysfunction of these miRNAs (and therefore the targets they regulate) may contribute to endometrial-derived recurrent pregnancy loss in women.
2023-05-10 | PXD036109 | Pride
Project description:The objective of this study was the identification of serum microRNAs that can differentiate osteoporotic fracture patients with and without type-2 diabetes from healthy control subjects. For that purpose circulating microRNAs were profiled by real-time quantitative PCR using a custom 384-well panel in 200 µl serum samples. Univariate and multivariate statistical tools were used in order to identify single as well as combinations of circulating microRNas that were characteristic of patients with prevalent osteoporotic fractures: a qRT-PCR-based classifier consisting of miR-550a-5p, miR-96-5p, miR-32-3p and miR-486-5p can distinguish T2D women with (DMFx) and without fragility fractures (DM) with high specifitiy and sensitivity (AUC = 0.93). A classifier consisting of miR-188-3p, miR-382-3p, miR-942 and miR-155-5p was capable of differentiating between postmenopausal women with osteoporotic fractures and fracture-free controls with an AUC of 0.98.
2016-12-31 | GSE70318 | GEO
Project description:Background: The identification of new high sensitivity and specificity markers for HCC are essential. We aimed to identify serum microRNAs for diagnosing hepatitis B virus (HBV) â??related HCC. Methods: Serum microRNA expression was investigated with four cohorts including 667 participants (261 HCC patients ,233 cirrhosi patients and 173 healthy controls), recruited between August 2010 and June 2013. First, An initial screening of miRNA expression by Illumina sequencing was performed using serum samples pooled from HCC patients and controls,respectively. Quantitative reverse-transcriptase polymerase chain reaction assay was then applied to evaluate the expression of selected microRNAs. A logistic regression model was constructed using a training cohort (n=357) and then validated using a cohort(n=241). The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. Results: , We identified 8 miRNAs(hsa-miR-206, hsa-miR-141-3p, hsa-miR-433-3p, hsa-miR-1228-5p, hsa-miR-199a-5p, hsa-miR-122-5p, hsa-miR-192-5p and hsa-miR-26a-5p.) formed a miRNA panel that provided a high diagnostic accuracy of HCC (AUC=0.887 and 0.879 for training and validation data set, respectively). The microRNA panel can also differentiate HCC from healthy (AUC =0.894) and cirrhosis (AUC = 0.892), respectively. Conclusions:We found a serum microRNAs panel that has considerable clinical value in diagnosing HCC. 9 serum samples pooled from 3 healthy control donors and 3 HCC patients, 3 cirrhosi patients treated at The First Affiliated Hospital of Soochow University were subjected to Illumina HiSeq 2000 deep sequencing to identify the miRNAs that were significantly differentially expressed.
2015-12-20 | E-GEOD-59418 | biostudies-arrayexpress