Plasma hsa-mir-19b is a potential LevoDopa therapy marker.
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ABSTRACT:
SUBMITTER: Chis AR
PROVIDER: S-EPMC8435426 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Lung cancer is a complex disease that often manifests at the point when treatment is not effective. Introduction of blood-based complementary diagnostics using molecular markers may enhance early detection of this disease and help reduce the burden of lung cancer. Here we evaluated the diagnostic potential of seven plasma miRNA biomarkers (miR-21, -19b, -126, -25, -205, -183, -125b) by quantitative reverse transcription PCR. Influence clinical and demographical characteristics, including age, tumor stage and cancer subtype on miRNA levels was investigated. Four miRNAs were significantly dysregulated (miR-19b, -21, -25, -183) in lung cancer patients. Combination of miR-19b and miR-183 provided detection of lung cancer with 94.7% sensitivity and 95.2% specificity (AUC = 0.990). Thus, miRNAs have shown the potential to discriminate histological subtypes of lung cancer and reliably distinguish lung cancer patients from healthy individuals.
| S-EPMC5074500 | biostudies-literature
Project description:BackgroundDiagnosis of pancreatic cancer (Pca) is challenging. This study investigated the value of plasma-derived exosome miR-19b (Exo-miR-19b) in diagnosing patients with Pca.MethodsPlasma was collected from 62 patients with Pca, 30 patients with other pancreatic tumor (OPT), 23 patients with chronic pancreatitis (CP), and 53 healthy volunteers. MiR-19b levels in plasma-derived exosomes were detected.ResultsPlasma-derived Exo-miR-19b levels normalized using miR-1228 were significantly lower in Pca patients than in patients with OPT, CP patients, and healthy volunteers. The diagnostic values of Exo-miR-19b normalized using miR-1228 were superior to those of serum cancer antigen 19-9 (CA19-9) in differentiating Pca patients from healthy volunteers (area under the curve (AUC): 0.942 vs. 0.813, p = 0.0054), potentially better than those of CA19-9 in differentiating Pca patients from CP patients (AUC: 0.898 vs. 0.792, p = 0.0720), and equivalent to those of CA19-9 in differentiating Pca patients from patients with OPT (AUC: 0.810 vs. 0.793, p = 0.8206). When normalized using Caenorhabditis elegans miR-39 (cel-miR-39), Exo-miR-19b levels in Pca patients were significantly higher than those in patients with OPT, CP patients, and healthy volunteers. The diagnostic values of Exo-miR-19b normalized using cel-miR-39 were equivalent to those of CA19-9 in differentiating Pca patients from healthy volunteers (AUC: 0.781 vs. 0.813, p = 0.6118) and CP patients (AUC: 0.672 vs. 0.792, p = 0.1235), while they were inferior to those of CA19-9 in differentiating Pca patients from patients with OPT (AUC: 0.631 vs. 0.793, p = 0.0353).ConclusionPlasma-derived Exo-miR-19b is a promising diagnostic marker for Pca. The diagnostic value of plasma-derived Exo-miR-19b normalized using miR-1228 is superior to that of serum CA19-9 in differentiating patients with Pca from healthy volunteers.
| S-EPMC8473875 | biostudies-literature
Project description:This SuperSeries is composed of the following subset Series: GSE22790: Gene expression after treatment with anti-miR-191 or control GSE22793: miR expression after treatment with anti-miR-191 or control GSE22909: Influence of TCDD onto HCC cell line Refer to individual Series
2011-07-01 | E-GEOD-22910 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2011-07-01 | GSE22910 | GEO
Project description:Sudden cardiac death due to ventricular arrhythmias often caused by action potential duration (APD) prolongation is a common mode of death in heart failure (HF). microRNAs, noncoding RNAs that fine tune gene expression, are frequently dysregulated during HF, suggesting a potential involvement in the electrical remodeling process accompanying HF progression. Here, we identified miR-19b as an important regulator of heart function. Zebrafish lacking miR-19b developed severe bradycardia and reduced cardiac contractility. miR-19b deficient fish displayed increased sensitivity to AV-block, a characteristic feature of long QT syndrome in zebrafish. Patch clamp experiments from whole hearts showed that miR-19b deficient zebrafish exhibit significantly prolonged ventricular APD caused by impaired repolarization. We found that miR-19b directly and indirectly regulates the expression of crucial modulatory subunits of cardiac ion channels, and thereby modulates AP duration and shape. Interestingly, miR-19b knockdown mediated APD prolongation can rescue a genetically induced short QT phenotype. Thus, miR-19b might represent a crucial modifier of the cardiac electrical activity, and our work establishes miR-19b as a potential candidate for human long QT syndrome.
| S-EPMC5090966 | biostudies-literature
Project description:Neuropathic pain in spinal cord injury (SCI) is associated with inflammation in both the peripheral and central nervous system (CNS), which may contribute to the initiation and maintenance of persistent pain. An understanding of factors contributing to neuroinflammation may lead to new therapeutic targets for neuropathic pain. Moreover, novel circulating biomarkers of neuropathic pain may facilitate earlier and more effective treatment. MicroRNAs (miRNAs) are short, non-coding single-stranded RNA that have emerged as important biomarkers and molecular mediators in physiological and pathological conditions. Using a genome-wide miRNA screening approach, we studied differential miRNA expression in plasma from 68 healthy, community-dwelling adults with and without SCI enrolled in ongoing clinical studies. We detected 2367 distinct miRNAs. Of these, 383 miRNAs were differentially expressed in acute SCI or chronic SCI versus no SCI and 71 were differentially expressed in chronic neuropathic pain versus no neuropathic pain. We selected homo sapiens (hsa)-miR-19a-3p and hsa-miR-19b-3p for additional analysis based on p-value, fold change, and their known role as regulators of neuropathic pain and neuroinflammation. Both hsa-miR-19a-3p and hsa-miR-19b-3p levels were significantly higher in those with chronic SCI and severe neuropathic pain versus those with chronic SCI and no neuropathic pain. In confirmatory studies, both hsa-miR-19a-3p and hsa-miR-19b-3p have moderate to strong discriminative ability to distinguish between those with and without pain. After adjusting for opioid use, hsa-miR-19b-3p levels were positively associated with pain interference with mood. Because hsa-miR-19 levels have been shown to change in response to exercise, folic acid, and resveratrol, these studies suggest that miRNAs are potential targets of therapeutic interventions.
| S-EPMC8570675 | biostudies-literature
Project description:Diabetic cardiomyopathy is characterized by metabolic changes in the myocardium that promote a slow and silent dysfunction of muscle fibers, leading to myocardium remodelling and heart failure, independently of the presence of coronary artery diseases or hypertension. At present, no imaging methods allow an early diagnosis of this disease. Circulating miRNAs in plasma have been proposed as biomarkers in the prognosis of several cardiac diseases. This study aimed to determine whether circulating miRNAs could be potential biomarkers of diabetic cardiomyopathy. Mice that were fed with a high fat diet for 16 months, showed metabolic syndrome manifestations, cardiac hypertrophy (without hypertension) and a progressive cardiac function decline. At 16 months, when maximal degree of cardiac dysfunction was observed, 15 miRNAs from a miRNA microarray screening in myocardium were selected. Then, selected miRNAs expression in myocardium (at 4 and 16 months) and plasma (at 4, 12 and 16 months) were measured by RT-qPCR. Circulating miR-19b-3p and miR-181b-5p levels were associated with myocardium levels during the development of diabetic cardiomyopathy (in terms of cardiac dysfunction), suggesting that these miRNAs could be suitable biomarkers of this disease in asymptomatic diabetic patients.
| S-EPMC5647433 | biostudies-literature
Project description:BackgroundChronic Fatigue Syndrome (CFS/ME) is a complex multisystem disease of unknown aetiology which causes debilitating symptoms in up to 1% of the global population. Although a large cohort of genes have been shown to exhibit altered expression in CFS/ME patients, it is currently unknown whether microRNA (miRNA) molecules which regulate gene translation contribute to disease pathogenesis. We hypothesized that changes in microRNA expression in patient leukocytes contribute to CFS/ME pathology, and may therefore represent useful diagnostic biomarkers that can be detected in the peripheral blood of CFS/ME patients.MethodsmiRNA expression in peripheral blood mononuclear cells (PBMC) from CFS/ME patients and healthy controls was analysed using the Ambion Bioarray V1. miRNA demonstrating differential expression were validated by qRT-PCR and then replicated in fractionated blood leukocyte subsets from an independent patient cohort. The CFS/ME associated miRNA identified by these experiments were then transfected into primary NK cells and gene expression analyses conducted to identify their gene targets.ResultsMicroarray analysis identified differential expression of 34 miRNA, all of which were up-regulated. Four of the 34 miRNA had confirmed expression changes by qRT-PCR. Fractionating PBMC samples by cell type from an independent patient cohort identified changes in miRNA expression in NK-cells, B-cells and monocytes with the most significant abnormalities occurring in NK cells. Transfecting primary NK cells with hsa-miR-99b or hsa-miR-330-3p, resulted in gene expression changes consistent with NK cell activation but diminished cytotoxicity, suggesting that defective NK cell function contributes to CFS/ME pathology.ConclusionThis study demonstrates altered microRNA expression in the peripheral blood mononuclear cells of CFS/ME patients, which are potential diagnostic biomarkers. The greatest degree of miRNA deregulation was identified in NK cells with targets consistent with cellular activation and altered effector function.
| S-EPMC4788442 | biostudies-literature
Project description:BackgroundGestational diabetes mellitus (GDM) is pregnancy-related diabetes with vital risks for both mother and the fetus. Molecular studies represent one of the popular approaches for investigating mechanisms associated with the disease nature. One of which is through interaction network analysis via Cytoscape V. 3.6.1.MethodsIn this study, the microRNA (miRNA) expression array of GSE98043 from gene expression omnibus (GEO) database was retrieved and screened. We identified 12 differentially expressed (DE) miRNAs (P ≤ 0.05) and nine target hub-bottleneck genes (disease score > 1) for GDM based on miRNA-target interactions created via plugin ClueGO + Cluepedia + STRING.ResultsMiRNA-target information showed that the miRNAs are mostly up-regulated and hsa-miR-145-5p and hsa-miR-875-5p targets the most genes. Among target genes, IL6, GCG, APOB, and ALB have the highest associations with DE-miRNAs. Gene ontology analysis based on biological processes identification via ClueGO + CluePedia, in addition, showed that target hub-bottlenecks are mainly related to metabolism functions and any changes in this regulatory network could impose fundamental alterations in these processes.ConclusionsIt can be concluded that via these introduced miRNAs and their targets, the molecular tests for diagnosis and treatment of GDM can be improved after applying validation approaches.
| S-EPMC6678685 | biostudies-literature
Project description:Prostate cancer (PCa) is the most commonly diagnosed male malignancy worldwide. Early diagnosis and metastases detection are crucial features to diminish patient mortality. High fat diet (HFD) and metabolic syndrome increase PCa risk and aggressiveness. Our goal was to identify miRNAs-based biomarkers for PCa diagnosis and prognosis associated with HFD. Mice chronically fed with a HFD or control diet (CD) were subcutaneously inoculated with androgen insensitive PC3 cells. Xenografts from HFD-fed mice showed increased expression of 7 miRNAs that we named "candidates" compared to CD-fed mice. These miRNAs modulate specific metabolic and cancer related pathways. Using bioinformatic tools and human datasets we found that hsa-miR-19b-3p and miR-101-3p showed more than 1,100 validated targets involved in proteoglycans in cancer and fatty acid biosynthesis. These miRNAs were significantly increased in the bloodstream of PCa patients compared to non-PCa volunteers, and in prostate tumors compared to normal adjacent tissues (NAT). Interestingly, both miRNAs were also increased in tumors of metastatic patients compared to tumors of non-metastatic patients. Further receiver-operating characteristic (ROC) analysis determined that hsa-miR-19b-3p and hsa-miR-101-3p in serum showed poor predictive power to discriminate PCa from non-PCa patients. Hsa-miR-19b-3p showed the best score to discriminate between tumor and NAT, while hsa-miR-101-3p was useful to differentiate between metastatic and non-metastatic PCa patients. Hsa-miR-101-3p was increased in exosomes isolated from blood of PCa patients. Although more detailed functional exploration and validation of the molecular mechanisms are required, we identified hsa-miR-19b-3p and hsa-miR-101-3p with high potential for PCa diagnosis and prognosis.
| S-EPMC8263646 | biostudies-literature