Author Correction: Differential expression of circulating exosomal microRNAs in refractory intracranial atherosclerosis associated with antiangiogenesis.
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ABSTRACT:
SUBMITTER: Jiang H
PROVIDER: S-EPMC8295272 | biostudies-literature | 2021 Jul
REPOSITORIES: biostudies-literature
Publications
Author Correction: Differential expression of circulating exosomal microRNAs in refractory intracranial atherosclerosis associated with antiangiogenesis.
Jiang Hao H Toscano Juan F JF Song Shlee S SS Schlick Konrad H KH Dumitrascu Oana M OM Pan Jianwei J Lyden Patrick D PD Saver Jeffrey L JL Gonzalez Nestor R NR
Scientific reports 20210721 1
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Project description:Purpose:We aimed to investigate the role of circulating exosomal microRNAs (e-miRNAs) in recurrent ischemic events in ICAD Methods: consecutive patients with severe ICAD undergoing intensive medical management (IMM) were prospectively enrolled. Those with recurrent ischemic events despite IMM during 6-month follow up were algorithmically matched to IMM responders. Baseline blood e-miRNA expression levels of the matched patients were measured using next generation sequencing Results: a total of 122 e-miRNAs were isolated from blood samples of 10 non-responders and 11 responders. Thirteen e-miRNAs predicted IMM failure with 90% sensitivity and 100% specificity. Ingenuity pathway analysis (IPA) determined 10 of the 13 e-miRNAs were significantly associated with angiogenesis-related biological functions (p < 0.025) and angiogenic factors that have been associated with recurrent ischemic events in ICAD. These e-miRNAs included miR-122-5p, miR-192-5p, miR-27b-3p, miR-16-5p, miR-486-5p, miR-30c-5p, miR-10b-5p, miR-10a-5p, miR-101-3p, and miR-24-3p. As predicted by IPA, the specific expression profiles of these 10 e-miRNAs in non-responders had a net result of inhibition of the angiogenesis-related functions and up expression of the antiangiogenic factors conclusion: This study revealed distinct expression profiles of circulating e-miRNAs in refractory ICAD, suggesting an antiangiogenic mechanism underlying IMM failure.
2021-06-21 | GSE178500 | GEO
Project description:Differential expression of circulating exosomal microRNAs in refractory intracranial atherosclerosis associated with antiangiogenesis
| PRJNA739407 | ENA
Project description:Intracranial atherosclerotic disease (ICAD) is one of the most common causes of stroke worldwide and the one with the worst prognosis. In this study, we assessed the hypothesis that the balance of circulating pro- and antiangiogenic factors plays a role in the evolution of the disease and can be used as a potential marker for the disease course and a target for treatment. Seventy-four patients with severe ICAD were enrolled in this prospective observational study, medically optimized, and followed for 6 months. Thirteen pro- and eight antiangiogenic factors were measured in the participants' serum using a sandwich multiplex ELISA. Angiogenic profiles were calculated using principal component analysis. We tested the association between angiogenic profiles and recurring cerebrovascular events despite intensive medical therapy, disability at 6 months after enrollment, and angiographic neovascularization in patients who failed medical treatment and underwent indirect revascularization surgery. There is a strong association between a functionally antiangiogenic profile and recurrent stroke or TIA in patients with ICAD (OR = 7.2, CI 2.4-34.4). Multivariable regression analysis showed that this antiangiogenic profile was also associated with poor functional status after 6 months (p = 0.002), independent from other clinical features such as history of previous stroke, diabetes, and age. In patients who failed medical management and underwent indirect revascularization surgery, high endostatin and angiostatin levels were also associated with low angiographic neovascularization (p = 0.02). The results of this study point to the striking importance of antiangiogenesis as a determinant of ICAD patient prognosis and suggest a possible new target for therapy.
| S-EPMC5831393 | biostudies-literature
Project description:Background: Intracranial atherosclerosis (ICAS) is a major cause of ischemic stroke, yet fundamental studies regarding epigenetic regulation of ICAS are lacking. We hypothesized that, due to anatomical and/or functional differences, extracranial atherosclerosis is distinct from ICAS, which may explain the clinical variability as well. Methods: We chose a number of miRNAs involved in various steps of atherogenesis (namely, miR-712/205-5p/-3p, miR-106b-3p/-5p, miR-146a-3p/-5p, miR-100-3p/miR-5p, miR-200c-3p/-5p, miR-532-3p/-5p, and miR-126-3p/-5p) and examined their plasma levels in a cohort of patients with carotid stenosis > 50% (n = 35, mean age: 65 years, 54% male; 12 patients had ICAS). Results: A differential pattern of circulating miR expression was found in ICAS patients: there was an overexpression of miR-712/205-5p, miR-106b-5p, miR-146a-5p, miR-200c-5p, miR-532-3p, and miR-126-3p. The following miRs were underexpressed in intracranial atherosclerosis-miR-712/205-3p and miR-100-3p. These changes represent a plethora of atherogenic mechanisms: smooth muscle cell migration (miR-712/205, miR-532), foam cell formation (miR-106b, miR-146a), endothelial dysfunction (miR-200c), low-density lipoprotein-induced vascular damage (miR-100), and leukocyte recruitment (miR-126). In symptomatic ICAS patients, we observed a statistically significant upregulation of miR-712/205-3p and miR-146a-5p. Conclusions: Overall, the findings of our pilot study revealed several new and interesting associations: (1) intracranial atherosclerosis seems to have a different epigenetic profile (regarding circulating microRNA expression) than isolated extracranial vessel involvement; (2) ischemic stroke in ICAS may be potentiated by other pathophysiologic mechanisms than in extracranial-only atherosclerosis (ECAS). Certain miRs (e.g., miR-712/205) seem to have a larger impact on ICAS than on extracranial atherosclerosis; this may be potentially linked to difference between extra- and intracranial artery morphology and physiology, and/or may lead to the said differences. This underscores the importance of making a distinction in future epigenetic studies between ECAS and ICAS, as the mechanisms of atherogenesis are likely to vary.
| S-EPMC11853257 | biostudies-literature
Project description:Circulating microRNAs (c-miRNAs) are associated with physiological adaptation to acute and chronic aerobic exercise in humans. To investigate the potential effect of grazing movement on miRNA circulation in cattle, here we profiled miRNA expression in centrifugally prepared exosomes from the plasma of both grazing and housed Japanese Shorthorn cattle. Microarray analysis of the c-miRNAs resulted in detection of a total of 231 bovine exosomal miRNAs in the plasma, with a constant expression level of let-7g across the duration and cattle groups. Expression of muscle-specific miRNAs such as miR-1, miR-133a, miR-206, miR-208a/b, and miR-499 were undetectable, suggesting the mildness of grazing movement as exercise. According to validation by quantitative RT-PCR, the circulating miR-150 level in the grazing cattle normalized by the endogenous let-7g level was down-regulated after 2 and 4 months of grazing (P < 0.05), and then its levels in housed and grazing cattle equalized when the grazing cattle were returned to a housed situation. Likewise, the levels of miR-19b, miR-148a, miR-221, miR-223, miR-320a, miR-361, and miR-486 were temporarily lowered in the cattle at 1 and/or 2 month of grazing compared to those of the housed cattle (P < 0.05). In contrast, the miR-451 level was up-regulated in the grazing cattle at 2 months of grazing (P = 0.044). The elevation of miR-451 level in the plasma was coincident with that in the biceps femoris muscle of the grazing cattle (P = 0.008), which suggests the secretion or intake of miR-451 between skeletal muscle cells and circulation during grazing. These results revealed that exosomal c-miRNAs in cattle were affected by grazing, suggesting their usefulness as molecular grazing markers and functions in physiological adaptation of grazing cattle associated with endocytosis, focal adhesion, axon guidance, and a variety of intracellular signaling, as predicted by bioinformatic analysis.
| S-EPMC4550388 | biostudies-literature
Project description:IntroductionWe compared circulating microRNA (miRNA) levels in plasma of patients with intracranial aneurysms (IA) to those of controls as a first step towards finding potential biomarkers for individuals at high risk of IA development and its subsequent rupture.Patients and methodsUsing a PCR array we measured 370 miRNAs in plasma of 15 patients with prior aneurysmal subarachnoid hemorrhage (aSAH), of whom 11 had an additional unruptured IA (UIA), and of 15 controls. MiRNAs with a difference in levels with an absolute fold change (FC) > 1.2 and p<0.01 were further tested using real-time (RT) PCR in an additional independent set of 15 aSAH patients, 15 untreated UIA patients and 15 controls for replication (absolute FC >1.2 and p<0.05). We used receiver operating characteristic (ROC) curves to illustrate the diagnostic potential of these miRNAs.ResultsThree of five miRNAs with a difference in levels in the PCR array study were replicated with miRNA-183-5p decreased in all patients (FC = -2.2, p = 1.7x10-3), miRNA-200a-3p increased in aSAH patients (FC = 1.8, p = 2.8x10-2) and miRNA-let7b-5p decreased in UIA patients (FC = -1.7, p = 1.27x10-3) as compared to controls. In distinguishing aSAH patients from controls, the area under the ROC curve (AUC) was 0.80 (95% confidence interval (95% CI) 0.63-0.97) for miRNA-183-5p, and 0.74 (95% CI 0.55-0.94) for miRNA-200a-3p. In distinguishing untreated UIA patients from controls, AUC was 0.83 (95% CI 0.69-0.98) for miRNA-183-5p and 0.92 (95% CI 0.81-1) for miRNA-let-7b.Discussion/conclusionsWe identified three specific circulating miRNAs that are able to discriminate between IA patients and controls. Follow-up studies should assess if these miRNAs may be used biomarkers for identifying individuals at high risk of IA development and its subsequent rupture.
| S-EPMC5411042 | biostudies-literature
Project description: Not available
| S-EPMC10665331 | biostudies-literature
Project description:PurposeExosomal microRNAs (miRNAs) have been attracting major interest as potential diagnostic biomarkers of cancer. The aim of this study was to characterize the miRNA profiles of serum exosomes and to identify those that are altered in colorectal cancer (CRC). To evaluate their use as diagnostic biomarkers, the relationship between specific exosomal miRNA levels and pathological changes of patients, including disease stage and tumor resection, was examined.Experimental designMicroarray analyses of miRNAs in exosome-enriched fractions of serum samples from 88 primary CRC patients and 11 healthy controls were performed. The expression levels of miRNAs in the culture medium of five colon cancer cell lines were also compared with those in the culture medium of a normal colon-derived cell line. The expression profiles of miRNAs that were differentially expressed between CRC and control sample sets were verified using 29 paired samples from post-tumor resection patients. The sensitivities of selected miRNAs as biomarkers of CRC were evaluated and compared with those of known tumor markers (CA19-9 and CEA) using a receiver operating characteristic analysis. The expression levels of selected miRNAs were also validated by quantitative real-time RT-PCR analyses of an independent set of 13 CRC patients.ResultsThe serum exosomal levels of seven miRNAs (let-7a, miR-1229, miR-1246, miR-150, miR-21, miR-223, and miR-23a) were significantly higher in primary CRC patients, even those with early stage disease, than in healthy controls, and were significantly down-regulated after surgical resection of tumors. These miRNAs were also secreted at significantly higher levels by colon cancer cell lines than by a normal colon-derived cell line. The high sensitivities of the seven selected exosomal miRNAs were confirmed by a receiver operating characteristic analysis.ConclusionExosomal miRNA signatures appear to mirror pathological changes of CRC patients and several miRNAs are promising biomarkers for non-invasive diagnosis of the disease.
| S-EPMC3976275 | biostudies-literature
Project description:ObjectiveDisruption in the delicate symphony of genes, microRNA (miRNA), or protein expression can result in the dysregulation of the immune system, leading to the devastating consequences such as lupus nephritis (LN). The capacity of exosomes to transport miRNAs between cells and modify the phenotype of recipient cells implies their involvement in persistent kidney inflammation. This study unveils identifying two previously undiscovered exosomal miRNAs in the serum of LN patients, offering potential solutions to the current challenges in LN diagnosis and management.MethodsInitially, we used a reagent-based kit to isolate serum exosomes from patients with Systemic lupus erythematosus (SLE) and used Trizol method for total RNA extraction. Subsequently, we employed small RNA sequencing to screen for differential expression profiles of exosomal small RNAs. The RT-qPCR method was used to individually validate samples in both the screening and validation cohorts, enabling the identification of candidate small RNAs; specific to LN. We assessed the diagnostic potency using receiver operating characteristic (ROC) curve, and explored the biological roles of miRNAs using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses.ResultsCompared to SLE patients without LN, SLE patients accompanied by LN exhibited significantly spiked levels of exosomal hsa-miR-4796-5p and hsa-miR-7974. The duo of miRNAs, hsa-miR-4796-5p and hsa-miR-7974, exhibited promising potential as biomarkers for diagnosing LN, with an AUC exceeding 0.8. Correlation analysis revealed a strong positive association between these miRNAs and proteinuria, as well as the SLE Disease Activity Index (SLEDAI) score. Moreover, the levels of two miRNAs in LN patients were significantly elevated in comparison to other autoimmune nephritis conditions, such as immunoglobulin A nephropathy (IgAN) and diabetic nephropathy (DN). Furthermore, the bioinformatics analysis indicated that this miRNAs duo can play a pivotal role in the regulation of immune processes by modulating signal pathways, such as the mTOR and PI3K-Akt signaling pathway.ConclusionThis study provides a new ground that serum exosomal miRNAs can effectively identify and predict LN in SLE patients.
| S-EPMC10785001 | biostudies-literature
Project description: Not available
| S-EPMC9515150 | biostudies-literature