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Background: Recently, circulating microRNAs (miRNAs) from maternal blood and amniotic fluid have been used as biomarkers for ventricular septal defect (VSD) diagnosis. However, whether circulating miRNAs are associated with fetal myocardium remains unknown. Methods: Dimethadione (DMO) induced a VSD rat model. The miRNA expression profiles of the myocardium, amniotic fluid and maternal serum were analyzed. Differentially expressed microRNAs (DE-microRNAs) were verified by qRT-PCR. The target gene of miR-1-3p was confirmed by dual luciferase reporter assays. Expression of amniotic fluid-derived DE-microRNAs was verified in clinical samples. Results: MiRNAs were differentially expressed in VSD fetal rats and might be involved in cardiomyocyte differentiation and apoptosis. MiR-1-3p, miR-1b and miR-293-5p were downregulated in the myocardium and upregulated in amniotic fluid/maternal serum. The expression of amniotic fluid-derived DEmicroRNAs (miR-1-3p, miR-206 and miR-184) was verified in clinical samples. Dual luciferase reporter assays confirmed that miR-1-3p directly targeted SLC8A1/NCX1. Conclusion: MiR-1-3p, miR-1b and miR-293-5p are downregulated in VSD myocardium and upregulated in circulation and may be released into circulation by cardiomyocytes. MiR-1-3p targets SLC8A1/NCX1 and participates in myocardial apoptosis. MiR-1-3p upregulation in circulation is a direct and powerful indicator of fetal VSD and is expected to serve as a prenatal VSD diagnostic marker. [ABSTRACT FROM AUTHOR]

Natalizumab (NTZ) can reactivate human polyomavirus John Cunningham polyomavirus (JCPyV) latent infection and lead to progressive multifocal leukoencephalopathy (PML). NTZ modulates the expression of microRNA-126-3p (miR-126-3p) and its target genes, Spi-B, POU2AF1 , and vascular cell adhesion molecule-1 (VCAM-1); Spi-B protein binds the JCPyV regulatory region, initiating early gene transcription. This paper is aimed to evaluate the miR-126-3p and soluble (s)VCAM-1 concentration, Spi-B / POU2AF1 gene expression, and JCPyV activity in patients with multiple sclerosis (MS) before and during 2-years NTZ. Serum miR-126-3p and sVCAM-1 concentration was measured before NTZ and after 1, 12, and 24 months of treatment in 22 MS subjects, 1 patient who developed PML, and 29 healthy controls (HCs). The Spi-B and POU2AF1 expression in blood was analyzed at baseline and at month 24 in 13 patients with MS; results were clusterized based on JCPyV activity. miR-126-3p was significantly downregulated in MS before and during NTZ but was greatly increased in the PML patient. sVCAM-1 concentration was comparable in MS and HCs, and was reduced by NTZ in MS and PML. Spi-B/POU2AF1 expression was significantly increased in MS at baseline and was upregulated by NTZ, particularly in JCPyV-infected patients in whom JCPyV reactivation was detected. Taken together, the results suggest that the modulation of the miR-126-3p/ POU2AF1/Spi-B axis associates with JCPyV activity in NTZ-treated patients with MS. [ABSTRACT FROM AUTHOR]

Natalizumab (NTZ) can reactivate human polyomavirus John Cunningham polyomavirus (JCPyV) latent infection and lead to progressive multifocal leukoencephalopathy (PML). NTZ modulates the expression of microRNA-126-3p (miR-126-3p) and its target genes, Spi-B, POU2AF1, and vascular cell adhesion molecule-1 (VCAM-1); Spi-B protein binds the JCPyV regulatory region, initiating early gene transcription. This paper is aimed to evaluate the miR-126-3p and soluble (s)VCAM-1 concentration, Spi-B/POU2AF1 gene expression, and JCPyV activity in patients with multiple sclerosis (MS) before and during 2-years NTZ. Serum miR-126-3p and sVCAM-1 concentration was measured before NTZ and after 1, 12, and 24 months of treatment in 22 MS subjects, 1 patient who developed PML, and 29 healthy controls (HCs). The Spi-B and POU2AF1 expression in blood was analyzed at baseline and at month 24 in 13 patients with MS; results were clusterized based on JCPyV activity. miR-126-3p was significantly downregulated in MS before and during NTZ but was greatly increased in the PML patient. sVCAM-1 concentration was comparable in MS and HCs, and was reduced by NTZ in MS and PML. Spi-B/POU2AF1 expression was significantly increased in MS at baseline and was upregulated by NTZ, particularly in JCPyV-infected patients in whom JCPyV reactivation was detected. Taken together, the results suggest that the modulation of the miR-126-3p/POU2AF1/Spi-B axis associates with JCPyV activity in NTZ-treated patients with MS.

Background: Circulating microRNAs (miRNAs) are emerging as promising biomarkers for cancer. The objective of the current study was to investigate the potential of circulating cell-free miRNAs as biomarkers for colorectal cancer (CRC) and its precursor lesion, colorectal adenoma.Methods: The serum levels of 800 miRNAs were assessed in a discovery set of 21 patients with CRC, 19 patients with adenoma, and 21 healthy controls using the NanoString miRNA analysis platform. Significantly differentially expressed miRNAs were examined further in a validation cohort of 34 patients with CRC, 33 patients with adenoma, and 35 healthy controls using Fluidigm quantitative polymerase chain reaction assays.Results: The ratios between the expression values of the differentially expressed miRNAs were computed. Three miRNA ratios (miR-17-5p/miR-135b, miR-92a-3p/miR135b, and miR-451a/miR-491-5p) were validated for discriminating patients with adenoma and those with CRC from the healthy control group, and 5 miRNA ratios (let-7b/miR-367-3p, miR-130a-3p/miR-409-3p, miR-148-3p/miR-27b, miR-148a-3p/miR-409-3p, and miR-21-5p/miR-367-3p) were validated for discriminating patients with CRC from those with adenoma and healthy controls. The area under the receiver operating characteristic curve values for the 3 miRNA ratios in discriminating patients with adenoma from healthy controls were 0.831 and 0.735, respectively, in the discovery and validation sets. The area under the receiver operating characteristic curve values for the 5 miRNA ratios in discriminating patients with CRC from those with adenoma were 0.797 and 0.732, respectively, in the discovery and validation sets. Pathway analysis revealed that target genes regulated by the miRNAs from the miRNA ratios were enriched mainly in metabolism-related and inflammation-related pathways.Conclusions: The data from the current study suggest that circulating miRNAs can distinguish patients with CRC and those with adenoma and may represent novel biomarkers for the early, noninvasive detection of CRC. Cancer 2018;124:785-96. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Osteoporosis is the consequence of altered bone metabolism resulting in the systemic reduction of bone strength and increased risk of fragility fractures. MicroRNAs (miRNAs) regulate gene expression on a post-transcriptional level and are known to take part in the control of bone formation and bone resorption. In addition, it is known that miRNAs are secreted by many cell types and can transfer “messages” to recipient cells. Thus, circulating miRNAs might not only be useful as surrogate biomarkers for the diagnosis or prognosis of pathological conditions, but could be actively modulating tissue physiology. Therefore, the aim of this study was to test whether circulating miRNAs that exhibit changes in recent osteoporotic fracture patients could be causally related to bone metabolism. In the first step we performed an explorative analysis of 175 miRNAs in serum samples obtained from 7 female patients with recent osteoporotic fractures at the femoral neck, and 7 age-matched female controls. Unsupervised cluster analysis revealed a high discriminatory power of the top 10 circulating miRNAs for patients with recent osteoporotic fractures. In total 6 miRNAs, miR-10a-5p, miR-10b-5p, miR-133b, miR-22-3p, miR-328-3p, and let-7g-5p exhibited significantly different serum levels in response to fracture (adjusted p-value < 0.05). These miRNAs were subsequently analyzed in a validation cohort of 23 patients (11 control, 12 fracture), which confirmed significant regulation for miR-22-3p, miR-328-3p, and let-7g-5p. A set of these and of other miRNAs known to change in the context of osteoporotic fractures were subsequently tested for their effects on osteogenic differentiation of human mesenchymal stem cells (MSCs) in vitro. The results show that 5 out of 7 tested miRNAs can modulate osteogenic differentiation of MSCs in vitro. Overall, these data suggest that levels of specific circulating miRNAs change in the context of recent osteoporotic fractures and that such perturbations of “normal” levels might affect bone metabolism or bone healing processes. [ABSTRACT FROM AUTHOR]

Background: Recently, circulating microRNAs (miRNAs) from maternal blood and amniotic fluid have been used as biomarkers for ventricular septal defect (VSD) diagnosis. However, whether circulating miRNAs are associated with fetal myocardium remains unknown. Methods: Dimethadione (DMO) induced a VSD rat model. The miRNA expression profiles of the myocardium, amniotic fluid and maternal serum were analyzed. Differentially expressed microRNAs (DE-microRNAs) were verified by qRT-PCR. The target gene of miR-1-3p was confirmed by dual luciferase reporter assays. Expression of amniotic fluid-derived DE-microRNAs was verified in clinical samples. Results: MiRNAs were differentially expressed in VSD fetal rats and might be involved in cardiomyocyte differentiation and apoptosis. MiR-1-3p, miR-1b and miR-293-5p were downregulated in the myocardium and upregulated in amniotic fluid/maternal serum. The expression of amniotic fluid-derived DE-microRNAs (miR-1-3p, miR-206 and miR-184) was verified in clinical samples. Dual luciferase reporter assays confirmed that miR-1-3p directly targeted SLC8A1/NCX1. Conclusion: MiR-1-3p, miR-1b and miR-293-5p are downregulated in VSD myocardium and upregulated in circulation and may be released into circulation by cardiomyocytes. MiR-1-3p targets SLC8A1/NCX1 and participates in myocardial apoptosis. MiR-1-3p upregulation in circulation is a direct and powerful indicator of fetal VSD and is expected to serve as a prenatal VSD diagnostic marker., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Yang, Lian, Yang, Shen, Wu, Wang and Lyu.)

Esophageal cancer is one of the deadliest cancers worldwide. It typically has a poor overall prognosis because of diagnosis in advanced stages. Sensitive biomarkers for the early detection of esophageal cancer are urgently needed to reduce the high mortality of this disease. Circulating microRNAs (miRNAs) are emerging as a novel non-invasive biomarker for cancer diagnosis due to its high stability and specificity. In this study, we profiled circulating miRNAs in serum of patients with esophageal adenocarcinoma (EAC) using the Solexa sequencing analysis. The analysis demonstrated marked differences of more than 195 circulating miRNAs including 96 of upregulated and 99 of downregulated miRNA in EAC patients compared with healthy subjects. Quantitative reverse transcription PCR verified that the concentrations of circulating miR-25-3p and miR-151a-3p were significantly elevated, while the concentrations of miR-100-5p and miR-375 were significantly decreased in EAC patients compared with healthy controls. These data indicate the profile of these 4 miRNAs may potentially serve as a serum biomarker to identify patients with EAC, and circulating miRNA profiling may be clinically useful for early detection or treatment response in EAC patients.