RNA-seq identifies circulating miR-125a-5p, miR-125b-5p and miR-143-3p as potential biomarkers for acute ischemic stroke
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ABSTRACT:
PROVIDER: PRJNA435535 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6761160.fastq.gz | Fastqsanger.gz | |||
| SRR6761170.fastq.gz | Fastqsanger.gz | |||
| SRR6761180.fastq.gz | Fastqsanger.gz | |||
| SRR6761190.fastq.gz | Fastqsanger.gz | |||
| SRR6761161.fastq.gz | Fastqsanger.gz |
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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:Sirtuins (SIRT) are NAD-dependent protein deacteylases and function in cellular metabolism, stress resistance, proliferation and disease. For SIRT7, a role in ribosomal gene transcription is proposed, but its function in cancer is currently unknown. In this study, we showed that SIRT7 expression was up-regulated in a large cohort of human hepatocellular carcinoma (HCC) patients, and that high expression of SIRT7 was associated with poor prognosis of HCC patients. Notably, inactivation of SIRT7 by siRNA suppressed tumor cell growth and caused G1/S cell cycle arrest in liver cancer cells. This treatment restored p21WAF1/Cip1 activity, induced Beclin-1 and autophagic gene expression and repressed cyclin D1. To explore mechanisms in SIRT7 regulation, microRNA (miRNA) profiling was carried out. This identified five significantly down-regulated miRNAs in HCC. Bioinformatic analysis of target sites and ectopic expression in HCC cells evidenced miR-125a-5p and miR-125b to suppress SIRT7 and cyclin D1 expression and to induce p21WAF1/Cip1-dependent G1 cell cycle arrest. Furthermore, treatment of HCC cells with 5-aza-2’-deoxycytidine or ectopic expression of wild-type but not mutated p53 restored miR-125a-5p and miR-125b expression and inhibited tumor cell growth to suggest their regulation by promoter methylation and p53 activity. To evidence clinical significance of these findings, mutations in the DNA binding domain of p53 and promoter methylation of miR-125b were investigated. Four out of nine patients with induced SIRT7 carried mutations in p53 gene and one patient showed hypermethylation of miR-125b promoter region. Conclusion: Our findings suggest that oncogenic potential of SIRT in hepatocarcinogenesis and that a regulatory loop is proposed whereby SIRT7 inhibits transcriptional activation of p21WAF1/Cip1 via repression of miR-125a-5p and miR-125b. This makes SIRT7 a promising target in cancer therapy.
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Project description:Breast cancer (BC) is a commonly identified life-threatening type of cancer and a major cause of death among women worldwide. Several microRNAs (miRs), including miR-143-5p, have been reported to be vital for regulating hallmarks of cancer; however, the effect of miR-143-5p on BC requires further exploration. The present study performed bioinformatics analysis on GSE42072 and GSE41922 datasets from the National Center for Biotechnology Information Gene Expression Omnibus (GEO) database to identify miR-143-5p expression patterns. Furthermore, miR-143-5p expression was detected in BC cell lines and tissues via reverse transcription-quantitative PCR. Post-transfection with miR-143-5p mimics, Cell Counting Kit-8, colony formation and Transwell assays were performed to explore the effects of miR-143-5p on BC cell proliferation, colony formation, and migration. The association of miR-143-5p with the hypoxia-inducible factor-1α (HIF-1α)-associated glucose transporter 1 (GLUT1) pathway was explored via western blotting, immunofluorescence and dual-luciferase reporter assay. The present study detected high expression of miR-143-5p in BC tissue of the GSE42072 and serum of the GSE41922 datasets by GEO chip analysis. Additionally, the expression levels of miR-143-5p were decreased in BC tissues compared with those in adjacent healthy tissues, and low miR-143-5p expression was associated with a poorer prognosis and shorter survival time in patients with BC. In vitro, miR-143-5p expression levels were decreased in BC cells, and transfection with miR-143-5p mimics suppressed BC cell proliferation, colony formation, migration. Furthermore, miR-143-5p targeted the HIF-1α-related GLUT1 pathway, and inhibited HIF-1α and GLUT1 expression. Additionally, HIF-1α agonists reversed the miR-143-5p-induced inhibition during tumorigenesis. In conclusion, miR-143-5p exhibited low expression in BC tissues, and suppressed BC cell proliferation, colony formation, migration. Moreover, the antitumor effects of miR-143-5p targeted the HIF-1α-related GLUT1 pathway.
2022-02-26 | E-MTAB-11160 | biostudies-arrayexpress
Project description:miR-125b-5p is a well known miRNA already describded in several forms of cancer. miR-125b-5p is expressed in adipose tissue, adipocytes as well as their precursor cells. We aim to invest the role of miR-125b-5p in white adipocytes conversion into brite adipocytes. To get an idea about putative targets of miR-125b-5p in adipocyte conversion, we transfected miR-125b-5p mimic in human Multipotent Adipose-Derived Stem (hMADS) cells, differenciated in white adipocytes. Gene expression profiling is performed 48h after hMADSC transfection. Two-condition experiment, hMADS cells at day 16 after conversion of white adipocytes into brite adipocytes, comparison of cells transfected with a mimic miR-125b-5p to cells transfected with a negative controle. Biological replicates: 4, indepently grown and harvested. On each array, one biological replicate of mimic miR-125b-5p transfected cells was directly compared to one biological replicate of mimic negative control transfected cells (serving as reference sample). All hybridizations were repeated with reversed dye assignment (dye-swap) as technical replicates.
2016-07-01 | E-GEOD-80816 | biostudies-arrayexpress
Project description:miR-125b-5p is a well known miRNA already describded in several forms of cancer. miR-125b-5p is expressed in adipose tissue, adipocytes as well as their precursor cells. We aim to invest the role of miR-125b-5p in white adipocytes conversion into brite adipocytes. To get an idea about putative targets of miR-125b-5p in adipocyte conversion, we transfected miR-125b-5p mimic in human Multipotent Adipose-Derived Stem (hMADS) cells, differenciated in white adipocytes. Gene expression profiling is performed 48h after hMADSC transfection.
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Project description:Illumina bead array data from TCAM2/14411H/2102EP cell lines for mRNA expression. Lines are treated with either MMC or a combination of miR-100-5p and miR-125b-5p (combo), RNA extracted at day2. There are also some untreated controls at day 7.
2024-03-01 | E-MTAB-13464 | biostudies-arrayexpress
Project description:To identify putative novel specific targets of miR-143-3p and miR-145-5p, we overexpressed these miRNAs in BRAFV600E mutant human M238P melanoma cells using synthetic mimics or a synthetic “negative” control mimic (miR-Neg). RNA samples were harvested 48 hours post-transfection and 2 independent experiments were carried out.
2021-12-29 | GSE171880 | GEO
Project description:Fused in sarcoma/translated in liposarcoma (FUS) is a causative gene of familial amyotrophic lateral sclerosis (fALS). Mutated FUS causes accumulation of DNA damage and stress granule (SG) formation, etc., thereby motor neuron (MN) death. However, key molecular aetiology of mutated FUS-dependent fALS (fALS-FUS) remains unclear. Here, both regular bioinformatics and Bayesian gene regulatory networks (GRN) analyses were applied to large-scale transcriptome datasets of induced pluripotent stem cell (iPSC)-derived MNs possessing wild-type form of FUS and mutated FUSH517D (FUSH517D MNs). From regular bioinformatics provided DNA damage response (DDR)-related genes were uniformly down-regulated in FUSH517D MNs. Bayesian GRN calculated by Super-Computer identified miR-125b-5p, TIMELESS and PRKDC as "hub genes/miRNA" which influence the GRNs. miR-125b-5p was up-regulated in FUSH517D MNs and negatively correlated with FUS, TIMELESS and miR-125b-5p target mRNAs. Introduction of miR-125b-5p suppressed Fus, Timeless and DDR-related genes in addition to miR-125b-5p targets in expression, and caused DNA damage. Furthermore, knocking-down Timeless expression caused DNA damage. PRKDC was down-regulated in FUSH517D MNs and the cellular model analyses validated DNA damage under impaired DNA-PK activity promoted FUS mis-localization to SGs. Collectively, our strategy with Bayesian GRNs based on the iPSC model would provide the first compelling evidence to elucidate fALS-FUSH517D molecular aetiology.
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Project description:Purpose: In recent years, research has revealed the role of microRNAs (miRs) as important regulators of endothelial function. Notably, miR-125a is upregulated in the blood of patients with acute vascular diseases. Since miRNAs act out their function in networks, we aimed at investigating the presence of a miR-125a-related network regulating the endothelial barrier. Method: We investigated transcriptional changes of human umbilical cord endothelial cells (HUVEC) after miR-125a overexpression in an acute inflammatory in-vitro setting using Next Generation Sequencing. Briefly, primary HUVECs from five different donors were transfected either with hsa-miR-125a-5p or negative control (NC). After transfection HUVECs were cultivated for 18 hours and stimulated with TNF (25 ng/ml) for additional 6 hours. We compared the following groups: NC (18047-0001, 18047-0002, 18047-0003, 18047-0004, 18047-0005) versus miR125a: (18047-0006, 18047-0007, 18047-0008, 18047-0009, 18047-0010) Results: MiR-125a overexpression in inflammatory activated HUVECs significantly altered gene expression of 468 genes (FC: +1.25 to -1.25 p<0.01). We found eight potential miR-125a direct target genes involved in endothelial barrier function.
2022-02-07 | GSE196161 | GEO
Project description:Fused in sarcoma/translated in liposarcoma (FUS) is a causative gene of familial amyotrophic lateral sclerosis (fALS). Mutated FUS causes accumulation of DNA damage and stress granule (SG) formation, etc., thereby motor neuron (MN) death. However, key molecular aetiology of mutated FUS-dependent fALS (fALS-FUS) remains unclear. Here, both regular bioinformatics and Bayesian gene regulatory networks (GRN) analyses were applied to large-scale transcriptome datasets of induced pluripotent stem cell (iPSC)-derived MNs possessing wild-type form of FUS and mutated FUSH517D (FUSH517D MNs). From regular bioinformatics provided DNA damage response (DDR)-related genes were uniformly down-regulated in FUSH517D MNs. Bayesian GRN calculated by Super-Computer identified miR-125b-5p, TIMELESS and PRKDC as "hub genes/miRNA" which influence the GRNs. miR-125b-5p was up-regulated in FUSH517D MNs and negatively correlated with FUS, TIMELESS and miR-125b-5p target mRNAs. Introduction of miR-125b-5p suppressed Fus, Timeless and DDR-related genes in addition to miR-125b-5p targets in expression, and caused DNA damage. Furthermore, knocking-down Timeless expression caused DNA damage. PRKDC was down-regulated in FUSH517D MNs and the cellular model analyses validated DNA damage under impaired DNA-PK activity promoted FUS mis-localization to SGs. Collectively, our strategy with Bayesian GRNs based on the iPSC model would provide the first compelling evidence to elucidate fALS-FUSH517D molecular aetiology.
2021-04-19 | GSE125652 | GEO