Serum miR-21 Research Articles

Expression and Clinical Significance of Serum MiR-370 and MiR-203 in Patients with Acute Myeloid Leukemia

To investigate the expression of microRNA-370 (miR-370) and microRNA-203 (miR-203) in the serum of patients with acute myeloid leukemia(AML), and to analyze its clinical diagnosis and prognostic significance. 57 patients with acute myeloid leukemia were enrolled as experimental group, and 21 healthy people were enrolled as control group. The fasting venous blood of the personal in the two groups were collected. The expression of miR-370 and miR-203 of the personal in each groups were detected by real-time fluorescent quantitative PCR. The receiver operating characteristic (ROC) curve was plotted to detected the diagnostic values of serum miR-370, miR-203, and the Kaplan-Meier method was used to estimate the relationship between expression and overall survival of the patients. Compared with healthy controls, serum miR-370 expression was significantly decreased in AML patients(P<0.05), and serum miR-203 expression was also significantly decreased (P<0.05). ROC curve analysis showed that the expression of serum miR-370 and miR-203 could be used to distinguish acute myeloid leukemia and healthy people. The area under the ROC curve of miR-370 was 0.909, and the sensitivity and specificity were 91.46% and 100.00%, respectively. The area under the ROC curve of miR-203 was 0.895, and the sensitivity and specificity were 83.45% and 89.71%, respectively. Serum levels of miR-370 and miR-203 were closely related to overall survival in AML patients. The expression of miR-370 and miR-203 is decreased in the serum of patients with AML and may be a new markers for the diagnosis and prognosis of AML.

Hematocrit-Related Alterations of Circulating microRNA-21 Levels in Heart Failure Patients with Reduced Ejection Fraction: A Preliminary Study.

Aim: Circulating microRNA-21 (miR-21) has been utilized as a diagnostic tool in the assessment of heart failure (HF). Blood constitution may be altered when HF occurs and miR-21 may affect hematopoiesis. Sample hemolysis may influence the determination of circulating miRNAs, challenging the diagnostic use of miRNAs. Methods: We examined the relationship between blood measurements and miR-21 levels in ambulant chronic HF patients with reduced ejection fraction (HFrEF; n = 19). Healthy volunteers (n = 11) served as controls. Serum miR-21 levels were measured through quantitative reverse transcription polymerase chain reaction (RT-qPCR) and we calculated the hemolysis score (H-score). Study was approved by an Institutional Review Board (EK FaF UK 02/2018). Results: MiR-21 serum levels were reduced in HFrEF patients compared with the controls (p < 0.05), without relationship to New York Heart Association class, left ventricular ejection fraction or N-terminal prohormone of brain natriuretic peptide levels. MiR-21 levels decreased markedly in anemic patients, compared with those with normal hematocrits (p < 0.05). We found a significant relationship between miR-21 to hematocrit (p < 0.05) and hemoglobin concentration (p < 0.05). Importantly, we found a correlation between hematocrit and sample H-score (p < 0.05) in the cohort of HFrEF patients; however, there was no correlation between hemolysis and miR-21. Conclusion: Circulating miR-21 levels were decreased in HFrEF patients and hematocrit was identified as a factor associated with this abnormality. This suggests that miR-21 mirrors other characteristics of HFrEF patients rather than the standard identifiers of HF severity and progression.

Circulating miR-155 and JAK2/STAT3 Axis in Acute Ischemic Stroke Patients and Its Relation to Post-Ischemic Inflammation and Associated Ischemic Stroke Risk Factors.

Background“Micro RNAs and their target genes recently have been identified to play a crucial role in the molecular pathogenesis of post-stroke ischemic cellular injury, which elucidates their new role in ischemic stroke diagnosis and therapy”. Thus, we evaluated the relative serum expression of miR-155, an inflammatory micro RNA, and the mRNAs (JAK2/STAT3) in acute ischemic stroke patients and its associations with the inflammatory cytokine TNF-α and different stroke risk factors.Subjects and MethodsThe relative expression of serum miR-155 and mRNAs (JAK2/STAT3) was assessed using RT-PCR, serum TNF-α was measured using ELIZA in 46 acute ischemic stroke patients and 50 control subjects. Receiver operating characteristic (ROC) curve was constructed to assess the specificity and sensitivity of circulating miR-155, JAK2/STAT3 as biomarkers for acute ischemic stroke.ResultsCirculating miR-155, JAK2/STAT3 were significantly up-regulated among stroke patients (8.5, 2.9, 4.2 fold respectively, P<0.001) with significant increase in TNF-α (263.8 ± 10.7 pg/mL, P <0.001). MiR-155, JAK2/STAT3 were positively correlated with TNF-α. MiR-155, JAK2/STAT3 were significantly increased in stroke patients and associated with risk factors such as hypertension, carotid atherosclerosis, and atrial fibrillation. Our study revealed that miR-155 has diagnostic accuracy for acute ischemic stroke where AUC=0.9, (P<0.001).ConclusionThe elevated expressions of circulating miR-155, JAK2/STAT3, and TNF-α in acute ischemic stroke patients could trigger post-stroke cellular inflammation. MiR-155 could be used as potential inflammatory biomarker for acute ischemic stroke. However, further clinical studies are still needed to determine the exact role of miRNAs and different signal transduction expressions in the stage of acute ischemic stroke.

Clinical significance of serum mir-21,ca153 and cea in breast cancer

The Objective: one of the essential regulators of carcinogenesis is MicroRNA-21 (miR-21). Yet little light has been shed on its effectiveness as a tumor marker compared to the conventional ones. Comparing the diagnostic value of established tumor markers in breast cancer (BC) such as carcinoembryonic antigen (CEA) and CA153 with circulating level of miR-21 is the aim of this study.Methods:The study included 89 BC patients. Amplification of the circulating levels of miR-21 and miR-16 done using real-time PCR qualitative detection, while electrochemiluminescence assays was used to detect circulating levels of CEA and CA153. The diagnostic sensitivity for BC was compared between the three.Results: The serum miR-21 levels were high significantly BC patients, as the latter had much higher levels (P&lt;0.001). the CA153 and CEA sensitivities were 15.73% and 22.47% respectively, while miR-21 Sensitivity and specificity were 87.6% and 87.3%.Conclusion:in BC patients miR-21 exhibits far higher sensitivity for diagnoses than both CEA and CA153. Thus especially in the early stages of BC, miR-21 can become a potential indicator for diagnosis, albeit the clinical stage, PR and ER statuses were not correlated in this study.

Assessing Determinants of the Current Account Deficit: A case study of India

The Objective: one of the essential regulators of carcinogenesis is MicroRNA-21 (miR-21). Yet little light has been shed on its effectiveness as a tumor marker compared to the conventional ones. Comparing the diagnostic value of established tumor markers in breast cancer (BC) such as carcinoembryonic antigen (CEA) and CA153 with circulating level of miR-21 is the aim of this study.Methods:The study included 89 BC patients. Amplification of the circulating levels of miR-21 and miR-16 done using real-time PCR qualitative detection, while electrochemiluminescence assays was used to detect circulating levels of CEA and CA153. The diagnostic sensitivity for BC was compared between the three.Results: the serum miR-21 levels were high significantly BC patients, as the latter had much higher levels (P&lt;0.001). the CA153 and CEA sensitivities were 15.73% and 22.47% respectively, while miR-21 Sensitivity and specificity were 87.6% and 87.3%.Conclusion:in BC patients miR-21 exhibits far higher sensitivity for diagnoses than both CEA and CA153. Thus especially in the early stages of BC, miR-21 can become a potential indicator for diagnosis, albeit the clinical stage, PR and ER statuses were not correlated in this study.

Serum miR-375 for Diagnostic and Prognostic Purposes in Medullary Thyroid Carcinoma.

PurposeHaving previously demonstrated that tissue miR-375 expression in medullary thyroid carcinoma (MTC) tissues is linked to prognosis, the aim of this study was to assess the diagnostic and prognostic value of circulating miR-375 levels in MTC patients.MethodsA series of 68 patients with MTC was retrospectively retrieved and assessed in terms of their clinicopathological characteristics. MiR-375 levels were measured in all patients’ presurgical blood samples. Both serum and tissue levels were tested prior to surgery in a subgroup of 57 patients. Serum miR-375 levels were also measured in serum from 49 patients with non-C-cell thyroid nodular diseases (non-CTN), 14 patients with pheochromocytoma, and 19 healthy controls.ResultsCirculating miR-375 levels were 101 times higher in the serum of patients with MTC than in all other patients and controls, with no overlap (P < 0.01). No correlation emerged between serum and tissue miR-375 levels. Serum miR-375 levels were higher in MTC patients with N0 than in those with N1 disease (P = 0.01), and also in patients who were biochemically cured than in those who were not (P = 0.02). In the whole series of patients and controls, calcitonin (CT) and serum miR-375 levels were correlated at diagnosis (R2 = 0.40, P < 0.01), but in a U-shaped manner: a positive correlation was found with low CT levels, then the correlation turns negative as CT rises (in MTC patients). A negative correlation was indeed found in MTC patients between serum miR-375 and CT (R2 = −0.10, P = 0.01). On ROC curve analysis, a cut-off of 2.1 for serum miR-375 proved capable of distinguishing between MTC patients and the other patients and controls with a 92.6% sensitivity and a 97.6% specificity (AUC: 0.978, P < 0.01).ConclusionsSerum miR-375 levels can serve as a marker in the diagnosis of MTC, with a remarkable specificity. Serum miR-375 also proved a novel marker of prognosis in this disease. Further in vitro experiments to corroborate our results are currently underway.

Profiling Tissue and Biofluid miR-155-5p, miR-155*, and miR-146a-5p Expression in Graft vs. Host Disease.

Introduction: Acute graft vs. host disease (aGvHD) is a frequent complication following allogeneic haematopoeitic transplantation (HSCT). Despite recent advances, there are no universally accepted biomarkers to determine development of aGvHD. MicroRNAs miR-146a and miR-155 have been previously associated with aGvHD and show promise as clinically translatable biomarkers. In this study, we performed comprehensive expression profiling of miR-146a, miR-155, and miR-155* expression in aGvHD target tissue and biofluids and relate expression to post-HSCT outcomes.Materials and Methods: MicroRNA expression was assessed by qRT-PCR in gastrointestinal (n = 31) and skin (n = 31) biopsies as well as serum (exploratory cohort n = 34, verification cohort n = 81, diagnostic cohort n = 65) and urine (exploratory cohort n = 30, verification cohort n = 56, diagnostic cohort n = 20) biofluids, including extracellular vesicle (EV) cohorts (serum EV n = 15, urine EV n = 30). Expression was related to aGvHD incidence, severity and overall survival.Results: In GI samples, expression of miR-155 (p = 0.03) and miR-146a (p = 0.03) was higher at aGvHD onset compared to patients with no GvHD. In skin biopsies, expression of miR-155 (p = 0.004) was upregulated in aGvHD patients compared to normal control skin. Expression of miR-146a was higher in aGvHD compared to no aGvHD biopsies (p = 0.002). In serum, miR-155 (p = 0.03) and miR-146a (p = 0.02) expression was higher at day 14 (D14), while in urine expression was elevated at D7 post-HSCT in patients who developed aGvHD compared to those disease-free. This was verified in an independent serum (miR-155 p = 0.005, miR-146a p = 0.003) and urine (miR-155 p = 0.02, miR-146a p = 0.04) cohort, where both microRNAs were also associated with aGvHD by ROC analysis. In serum and urine samples taken at the time of aGvHD symptoms, expression of miR-155 and miR-146a was also elevated (serum miR-155 p = 0.03, miR-146a p < 0.001; urine miR-155 p = 0.02, miR-146a p = 0.02). In contrast, miR-146a and miR-155 were downregulated at D14 in serum EVs and at D7 in urine EVs in patients who developed aGvHD compared to those that remained disease-free, in both an exploratory (serum miR-155 p = 0.02, miR-146a p = 0.06; urine miR-155 p = 0.02, miR-146a p = 0.07) and an independent cohort (serum miR-155 p = 0.01, miR-146a p = 0.02).Conclusions: These results further support a role for miR-155 and miR-146a as non-invasive, clinically relevant biomarkers for aGvHD. However, the link between their involvement in generalized inflammation and in specific pathophysiology requires further investigation at a systemic level.

Cell-free microRNA-1246 in different body fluids as a diagnostic biomarker for esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma is a malignant tumor with unfavorable prognosis. In this study, we investigated the usefulness of microRNA (miR)-1246 detection in various body fluids as a biomarker for this disease. A total of 72 patients with esophageal squamous cell carcinoma were enrolled, and their blood, urine, and saliva samples were collected prior to treatment. Reverse transcription–polymerase chain reaction of miR-1246 was performed, and pre- and postoperative and intraday fluctuations in its expression were examined. The expression of miR-1246 in the blood and urine was significantly higher in the patients with esophageal squamous cell carcinoma than in 50 healthy control subjects. Receiver operating characteristic curves showed that the area under the curve values were 0.91 (sensitivity 91.7%, specificity 76.0%), 0.82 (sensitivity 90.3%, specificity 62.0%), and 0.80 (sensitivity 83.3%, specificity 66.0%) in the serum, urine, and saliva, respectively. A relatively high diagnostic performance of miR-1246 was observed in all samples, which was better than that of the existing biomarkers squamous cell carcinoma antigen, carcinoembryonic antigen, and cytokeratin 19 fragment. No clear correlation was observed in the levels of miR-1246 expression among the three body fluids. Postoperatively, serum samples displayed significantly decreased miR-1246 levels. Although not significant, changes in the miR-1246 levels were observed at all collection times, with large fluctuations in the saliva. Meanwhile, serum miR-1246 expression was found to be associated with the disease prognosis. The results indicate that the levels of miR-1246 in the urine, saliva, and serum are a useful biomarker for esophageal squamous cell carcinoma and support the use of urine samples instead of blood samples for noninvasive diagnosis.

Circulating MicroRNAs and Long Non-coding RNAs as Potential Diagnostic Biomarkers for Parkinson's Disease.

Parkinson’s disease (PD) is the world’s second most common neurodegenerative disease that is associated with age. With the aging of the population, patients with PD are increasing in number year by year. Most such patients lose their ability to self-care with disease progression, which brings an incalculable burden to individual families and society. The pathogenesis of PD is complex, and its clinical manifestations are diverse. Therefore, it is of great significance to screen for circulating biomarkers associated with PD to reveal its pathogenesis and develop objective diagnostic methods so as to prevent, control, and treat the disease. In recent years, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are considered to be effective biomarkers for various diseases due to their stability, and resistance to RNAase digestion and extreme conditions in circulating fluids. Here, we review recent advances in the detection of abnormally expressed miRNAs and lncRNAs in PD circulating fluids, and discuss the function and molecular mechanisms of plasma or serum miR-124, miR-132, miR-29, miR-221, miR-7, miR-433, and miR-153 in the regulation and progression of PD. Additionally, application of the differential expression of lncRNAs in circulating fluid in the pathological progression and diagnosis of PD is also reviewed. In short, the determination of abnormally expressed circulating miRNAs and lncRNAs will be valuable for the future diagnosis and treatment of PD.

Role of serum miR-21 and miR-92a in colorectal cancer diagnosis as novel molecular biomarkers

Background: Our study aimed to evaluate the clinical utility of detecting plasma microRNAs (miR-21 & miR-92a) for diagnosis of colorectal cancer patients and its relation to tumor staging. Patients and Methods: Quantitative real-time RT-PCR was applied to determine the relative expression level of miR-21 and miR-92a in serum. The sensitivity and specificity of these markers were evaluated by receiver operating characteristic (ROC) curve analysis. Final staging of colorectal cancer cases was assigned according to results of histopathologic examination of surgically resected specimens. Results: This study included 52 cases of colorectal cancer (CRC), 20 cases of precancerous colorectal lesions, and 20 healthy controls. Both Plasma miR-21 and Plasma miR-92a were significantly higher in CRC group compared to both the control group and precancerous group. Also, they were significantly higher in advanced CRC stages than early CRC stages. The sensitivity and specificity of miR-21 for discriminating CRC from controls were found to be 90.38% and 100.0%, respectively. However, for miR-92a, sensitivity and specificity were found to be 94.23% and 100.0%, respectively. For discriminating CRC cases from precancerous lesions, the sensitivity and specificity of miR-21 were found to be 75.08% and 95.0%, respectively. However, for miR-92a, sensitivity and specificity were found to be 80.77% and 100.0%, respectively. Conclusions: both plasma miR-21 and miR-92a have significant value for early detection of CRC as non-invasive screening molecular biomarkers with high sensitivity and specificity. They also help for differentiation between patients with benign and malignant colorectal lesions and those with early and advanced CRC.

Expression of Serum miR-155 in Children with Mycoplasma pneumoniae Pneumonia and Its Role in Immunity to Mycoplasma pneumoniae.

ObjectiveTo investigate the expression of serum miR-155 in children with Mycoplasma pneumoniae pneumonia (MPP).MethodsA total of 100 children at our hospital with pneumonia caused by Mycoplasma pneumoniae infection were enrolled as a study group, including 45 cases in the acute phase (acute phase group) and 55 in the recovery phase (recovery phase group). An additional 30 healthy children were enrolled during the same period as the control group. The expression levels of miR-155, tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), IL-10, IL-13, immunoglobulin (Ig) G, IgA, complements (C3 and CH50), and T lymphocyte subsets (CD3+, CD4+, CD8+, and CD4+/CD8+) were determined. Multivariate logistic regression analysis was performed to identify risk factors affecting MPP in children.ResultsmiR-155, IL-10, IgG, IgA, CD3+, CD4+, and CD4+/CD8+ were poorly expressed in children with MPP, and their expression in the acute phase group was significantly lower than that in the recovery phase group. TNF-α, IL-13, C3, and CH50 were highly expressed in the children, and their expression was significantly higher in the acute phase group than in the recovery phase group. In the acute phase group, the expression of IL-8 was significantly higher than that in the control and recovery phase groups but without any significant differences between the recovery phase and control groups. Age, season, low complement state, epidemiological contact history, and antibiotic use time were independent risk factors affecting MPP in children.ConclusionSerum miR-155 is poorly expressed in children with MPP, and it can regulate inflammatory disorders and immune responses.

Evaluation of miR-122 Serum Level and IFN-λ3 Genotypes in Patients with Chronic HCV and HCV-Infected Liver Transplant Candidate.

Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are the most common markers of liver damage, but serum level interpretation can be complicated. In hepatocytes, microRNA-122 (miR-122) is the most abundant miRs and its high expression in the serum is a characteristic of liver disease. We aimed to compare the circulatory level of miR-122 in patients with Chronic Hepatitis C (CHC), Hepatitis C Virus (HCV) infected Liver Transplant Candidates (LTC) and healthy controls to determine if miR-122 can be considered as an indicator of chronic and advanced stage of liver disease. MiR-122 serum level was measured in 170 Interferon-naïve (IFN-naïve) CHC patients, 62 LTC patients, and 132 healthy individuals via TaqMan real-time PCR. Serum levels of miR-122 were normalized to the serum level of Let-7a and miR-221. Also, the ALT and AST levels were measured. ALT and AST activities and the expression of circulatory miR-122 were similar in the CHC and LTC groups, but it had significantly increased compared to healthy individuals (P<0.001 and P<0.001, respectively). Up-regulation of miR-122 in the sample of patients with normal ALT and AST activities was also observed, indicating that miR-122 is a good marker with high sensitivity and specificity for diagnosing liver damage. miR-122 seemed to be more specific for liver diseases in comparison with the routine ALT and AST liver enzymes. Since the lower levels of circulating miR-122 were observed in the LTC group compared to the CHC group, advanced liver damages might reduce the release of miR-122 from the hepatocytes, as a sign of liver function deficiency.

Dysregulation of lncRNA SNHG1/miR-145 axis affects the biological function of human carotid artery smooth muscle cells as a mechanism of carotid artery restenosis.

Carotid angioplasty and stenting have developed into reliable options for patients with carotid stenosis. However, postoperative restenosis remains a serious and unresolved problem. Restenosis is partly caused by the proliferation of vascular smooth muscle cells. As certain long non-coding RNAs (lncRNAs) affect cell proliferation and migration, the present study aimed to investigate them as novel biomarkers for restenosis development and to further reveal the potential underlying mechanisms. The expression of lncRNA small nucleolar RNA host gene 1 (SNHG1) and microRNA145 (miR-145) in human carotid artery smooth muscle cells (hHCtASMCs) was analyzed using reverse transcription-quantitative PCR. In addition, a luciferase reporter assay was performed to investigate the interaction between SNHG1 and miR-145. The effects of the SNHG1/miR-145 axis on the proliferation and migration of hHCtASMCs were evaluated by Cell Counting Kit-8 and Transwell assays. Serum SNHG1 and miR-145 expression levels were increased and decreased, respectively, in patients with restenosis (all P<0.001). High SNHG1 and low miR-145 were identified as risk factors for restenosis onset (all P<0.01). Furthermore, decreasing SNHG1 expression levels in hHCtASMCs inhibited cell proliferation and migration. The luciferase reporter assay and expression results demonstrated that miR-145 may be a target of SNHG1 and mediated the effects of SNHG1 on hHCtASMC proliferation and migration. The results obtained suggested that abnormal expression of SNHG1 and miR-145 may be risk factors for restenosis. The present study revealed that the SNHG1/miR-145 axis regulates hHCtASMC proliferation and migration, indicating its potential for restenosis prevention and treatment.

Preintervention MCP-1 serum levels as an early predictive marker of tumor response in patients with hepatocellular carcinoma undergoing transarterial chemoembolization.

BackgroundTransarterial chemoembolization (TACE) is a widely accepted treatment for unresectable or intermediate-stage hepatocellular carcinoma (HCC). However, response rates to TACE are heterogeneous and it is not fully understood which patients benefit most from TACE therapy in terms of tumor response. To identify the possible predictive roles of the perioperative monocyte chemoattractant protein-1 (MCP-1) levels in patients of HCC treated with TACE.MethodsForty patients of HCC receiving TACE were enrolled in a single center prospective observational study. MCP-1 and miR-210 levels were measured in 40 HCC patients at baseline before TACE and compared with 17 healthy controls by immunoassay and reverse transcriptase quantitative polymerase chain reaction (RT-qPCR). Tumor response assessments were taken after TACE treatment 4–6 weeks. Univariate and multivariate analysis were conducted to analyze factors correlated with tumor response in a Logistic regression model. The predictive roles of the involved variables on tumor response in patients with HCC suffering TACE were examined by receiver operating characteristic (ROC) curve analysis.ResultsThe serum MCP-1 and miR-210 levels were significantly elevated in HCC patients compared to healthy subjects. Patients with the low preintervention MCP-1 and miR-210 levels attained a higher probability of achieving an objective response (OR) (88.5% vs.42.9%, P=0.007; 76.9% vs. 35.7%, P=0.010, respectively). Pre-TACE MCP-1 level (<816.63 pg/mL) was an independent risk factor associated with OR after TACE by univariate and multivariate analysis while Pre-TACE miR-210 level (<4.43 relative expression) was just positive by univariate analysis. ROC curve analysis showed that a combined index based on those two factors exhibited optimal predictive power of tumor response among all the involved variables (area under the curve =0.823, 95% CI: 0.681–0.965). Additionally, high pre-TACE serum MCP-1 level was correlated with cirrhosis, vascular invasion and Barcelona Clinic Liver Cancer (BCLC) stage. Elevated pre-TACE serum miR-210 level was associated with and BCLC stage.ConclusionsThe study demonstrates that the pre-TACE serum MCP-1 level serves as an effective predictor for tumor response. These findings probably help discriminate HCC patients pre-TACE who specially benefit from TACE regarding OR.

Lead (Pb) exposure is associated with changes in the expression levels of circulating miRNAS (miR-155, miR-126) in Mexican women

The environmental contamination with lead (Pb) is considered a critical issue worldwide. Therefore, this study aimed to evaluate the expression levels of circulating miRNAs (miR-155, miR-126, and miR-145) in Mexican women exposed to Pb. Blood lead levels (BLL) were assessed in enrolled women (n = 190) using an atomic absorption method. Also, serum miRNAs expression levels were quantified through a real-time PCR assay. A mean BLL of 10.5 ± 4.50 μg/dL was detected. Overexpression of miR-155 was detected in highly exposed women. Besides, a significant simple positive relationship (p < 0.05) was found between BLL and serum miR-155 expression levels. Additionally, a significant inverse correlation (p < 0.05) was determined between BLL and serum miR-126 expression levels, as downregulation of miR-126 expression levels was observed in highly exposed women. The findings in this study are the concern, as epigenetic changes detected may represent a connection between health illnesses and Pb exposure.

Effects of miR-155 on High Glucose Induced-Cardiac Developmental Defects of Zebrafish Embryos

Background: Gestational diabetes mellitus (GDM) is known to have a teratogenic effect on heart development. Former studies determined that miR-155 is elevated in GDM patients. In the present study, we explored the potential role of miR-155 on high glucose-induced cardiac developmental defects. Methods: Serum miR-155 of GDM patients was determined by using ELISA. Fetal cardiac characteristics were collected by echocardiography. Zebrafish embryos were exposed to 2% D-Glucose in a fluctuating manner. The expression levels of miR-155, Ets1 and cardiac specific genes were evaluated by real-time PCR or western blot. Reactive oxygen species (ROS) were detected by DCFH-DA. Findings: High glucose exposure in zebrafish embryos altered the morphology of the heart, increased the expression of miR-155 and cardiac specific genes. Upregulation of miR-155 activated Igf1-Akt-Gsk3β pathway by targeting Ets1 and increased the production of ROS and may thereby exert teratogenic effect on cardiac development. Knockdown of miR-155 could rescue high glucose-induced zebrafish heart developmental defects. Besides, miR-155 levels are increased in serum from GDM patients and are correlated with fetal cardiac structural changes. Moreover, loss of miR-155 blocked Igf1 survival pathway and induced apoptosis and may thus cause zebrafish cardiac developmental defects. Interpretation: miR-155 is a key molecule for heart development and is involved in high glucose-induced cardiac malformation and it might be a novel biomarker as well as a potential drug target of high glucose-induced cardiac defects. Funding：This work was supported by grants from: (1) the Youth Program of National Natural Science Foundation (NSF)of China (81200125) to LY; (2) the Priority Academic Program Development (PAPD) and the Key Project of Natural Science Foundation of the Higher Education Institutions (17KJA310001) to LY; (3) the Six Talent Peaks Project (STPP) of Jiangsu Province (2015-WSN-032) to ZXT. Declaration of 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. Ethics Approval Statement: The studies involving human participants were reviewed and approved by Ethical Committee, Jiangsu province Hospital. The patients/participants provided their written informed consent to participate in this study. Zebrafish maintenance and procedures were conducted in accordance with the medical ethics committee of Nanjing Medical University. All experiments were approved by the medical ethics committee of Nanjing Medical University.

Four circulating exosomal miRNAs as novel potential biomarkers for the early diagnosis of human colorectal cancer

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. Our study aimed to identify novel circulating miRNAs as early diagnostic biomarkers of CRC. The Gene Expression Omnibus (GEO) datasets were analyzed by using the online tool GEO2R. Isolated exosomes were verified by using the transmission electron microscope (TEM), Nanosight, and western blot. qRT-PCR was implemented to examine miRNA expression. The diagnostic value of circulating exosomal miRNAs was identified by using the receiver operating characteristic curve (ROC). In this study, we found that serum exosomal miRNAs are more suitable for diagnosing CRC when compared to serum miRNAs. Furthermore, we identified four exosomal miRNAs (miR-126, miR-1290, miR-23a, and miR-940) in the serum of CRC patients as novel potential biomarkers for the early diagnosis of CRC because they showed high diagnostic values to differentiate CRC patients at TNM stage I from healthy controls (HCs). In addition, our data suggested that CRC cells may secrete miRNAs into the extracellular environment through exosomes regardless of intracellular miRNA expression. In conclusion, we identified serum exosomal miR-126, miR-1290, miR-23a, and miR-940 as novel potential biomarkers for the early diagnosis of CRC.

Circulating miR-148a-5p and miR-21-5p as Novel Diagnostic Biomarkers in Adult Egyptian Male Patients With Metabolic Syndrome

BackgroundMetabolic syndrome (MetS) is a group of abnormalities related to metabolism that increase the risk of cardiac diseases, type 2 diabetes and mortality. MicroRNAs (miRs) act as regulators of many cellular and metabolic events, and any dysregulation of these tiny molecules can cause great disturbance in one’s health. The main purpose of this study was to ascertain the diagnostic potential of miR-148a-5p and miR-21-5p in MetS. MethodsSerum levels of miR-148a-5p and miR-21-5p were quantified in 118 male patients with MetS and 30 healthy controls by quantitative real-time polymerase chain reaction. Fasting plasma glucose, serum high-density lipoprotein cholesterol and serum triacylglycerol were measured by the colorimetric method. Blood pressure and anthropometric measurements were performed on each individual. All MetS patients had diabetes and had a large waist circumference, and were divided into 3 groups: group 1, dyslipidemic and hypertensive; group 2, normotensive; and group 3, normal lipid profile.Results: miR-148a-5p expression was significantly upregulated in all MetS patients: group 1, 70.3±8.07 (p<0.0001); group 2, 75.0±9.17 (p<0.0001) and group 3, 33.7±6.89 (p<0.0001), when compared with control subjects. However, miR-21-5p expression was elevated only in the sera of group 1 (36.9±8.39, p<0.0001) and group 3 (48.9±12.0, p<0.0001), when compared with controls. ConclusionsSerum levels of miR-148a-5p and miR-21-5p were higher in MetS patients than in healthy controls; consequently, these serum miRs can serve as novel biomarkers for diagnosis and prognosis of MetS.

Prognostic markers for severity, activity, and recurrence of alopecia areata

Background Alopecia areata (AA) is considered an autoimmune disorder caused by altered T-cell-mediated immunity. MicroRNAs (miR) are important translational regulators of genes in various tissues and biological processes involved in autoimmune responses and have been identified in autoimmune diseases such as rheumatoid arthritis and type I diabetes mellitus. However, little is known about their role in pathogenesis of AA.Objective To assess serum levels of miR-155 and miR-146a in patients with AA and to correlate them with different clinical variables. Patients and methods MiR-155 and miR-146a serum levels were identified by real-time PCR in 50 patients with AA and 50 healthy age-matched and sex-matched patients as controls. Disease severity in the patients was assessed by Severity of Alopecia Tool score. Results There was a statistically significant increase in serum miR-155 and miR-146a levels in patients with AA than in controls. A significant increase in serum levels of miR-155 was found in patients with active disease and recurrent lesions of AA, whereas significant increase in serum level of miR-146a was found in patients with recurrent disease only. Significant positive correlations were found between serum miR-155 and miR-146a levels and disease severity. Conclusion Serum levels of miR-155 and miR-146a seem to have an essential role in the etiopathogenesis of AA and could be markers for severity and early detection of recurrent AA. In addition, serum miR-155 could be a marker of activity in AA, whereas serum miR-146a could be a marker of multiplicity. Further understanding of the function and regulation of miR-155 and miR-146a could be of great value for the introduction of new therapeutic approaches for AA.

Role of circulating micro-RNA-21 as a noninvasive biomarker for detection of colorectal cancer

ObjectiveTo assess serum micro-RNA-21 (miR-21) expression level as a stable blood-based biomarker for colorectal cancer (CRC).BackgroundCRC represents the third most common tumor worldwide with male predominance, with significant morbidity and mortality despite the recent therapeutic improvements. Therefore, a noninvasive diagnostic marker with good sensitivity and specificity is very important, which leads to better clinical outcomes. MiR-21 is an oncogenic miRNA that modulates the expression of multiple cancer-related target genes. MiR-21 expression was upregulated in the serum and in the malignant tissues in relation to the normal tissues. Its elevated level is claimed to be associated with poor survival and poor response to treatment.Patients and methodsThis cross-sectional study was carried on 50 patients and measured their serum miR-21 (CYBR Green). The cases group comprised 20 consecutive patients with CRC proved by colonoscopy and histopathological biopsy examination, the second group comprised 20 patients with colorectal polyps with no malignant transformation proved by histopathological examination, and the third group included 10 patients with normal colonoscopy finding as the control group. The studied cases were attending the Endoscopy Unit Menoufia University Hospital and Nasser Institute. The three groups agreed to written consent to participate in this study after the approval of the local ethical committee.ResultsSerum miR-21 expression was significantly upregulated in the cases group of patients with CRC compared with the other groups, with P value less than 0.001, showing sensitivity of 85% and specificity of 83.3% at a cutoff point of −2.31.ConclusionMi-RNA-21 shows upregulation in the serum in CRC cases, with statistically significant difference compared with the control group and the polyp group, showing promising results as a noninvasive biomarker of CRC.