Serum miR-122 Levels Research Articles

MiR-155 is involved in major depression disorder and antidepressant treatment via targeting SIRT1

Major depressive disorder (MDD) is a common mood disorder, and the treatment of MDD requires a variety of biopsychosocial approaches. The role of Silent information regulator 1 (SIRT1) in the regulation of MDD has recently been implicated. Here, we aimed to explore and elucidate the therapeutic effects of a microRNA, miR-155, in the treatment of MDD. With quantitative real-time PCR (qRT-PCR) analysis, we confirmed that cellular and serum levels of miR-155 were up-regulated in individuals with depression compared with those in healthy controls. TargetScan analysis indicated that SIRT1 is a target of miR-155, which was confirmed by dual-luciferase assay, qRT-PCR and Western blot analyses. Treatment of human neural progenitor cells with the antidepressant drug citalopram down-regulated miR-155 expression and up-regulated SIRT1 expression. These results suggest that miR-155 is an important factor in the pathophysiology of depression. miR-155 is a potential target for the development of new antidepressant treatments.

Serum miR-21 and miR-26a Levels Negatively Correlate with Severity of Cirrhosis in Patients with Chronic Hepatitis B.

Accurately evaluating the severity of liver cirrhosis is essential for clinical decision making and disease management. This study aimed to evaluate the value of circulating levels of microRNA (miR)-26a and miR-21 as novel noninvasive biomarkers in detecting severity of cirrhosis in patients with chronic hepatitis B. Thirty patients with clinically diagnosed chronic hepatitis B-related cirrhosis and 30 healthy individuals were selected. The serum levels of miR-26a and miR-21 were quantified by qRT-PCR. Receiver operating characteristic curve analysis was performed to evaluate the sensitivity and specificity of the miRNAs for detecting the severity of cirrhosis. Serum miR-26a and miR-21 levels were found to be significantly downregulated in patients with severe cirrhosis scored at Child-Pugh class C in comparison to healthy controls (miR-26a p<0.01, and miR-21 p<0.001, respectively). The circulating miR-26a and miR-21 levels in patients were positively correlated with serum albumin concentration but negatively correlated with serum total bilirubin concentration and prothrombin time. Receiver operating characteristic curve analysis revealed that both serum miR-26a and miR-21 levels were associated with a high diagnostic accuracy for patients with cirrhosis scored at Child-Pugh class C (miR-26a Cut-off fold change at ≤0.4, Sensitivity: 84.62%, Specificity: 89.36%, P<0.0001; miR-21 Cut-off fold change at ≤0.6, Sensitivity: 84.62%, Specificity: 78.72%, P<0.0001). Our results indicate that the circulating levels of miR-26a and miR-21 are closely related to the extent of liver decompensation, and the decreased levels are capable of discriminating patients with cirrhosis at Child-Pugh class C from the whole cirrhosis cases.

Serum exosomal miR-210 as a potential biomarker for clear cell renal cell carcinoma.

Exosomal microRNAs (miRNAs) are suggested to reflect molecular changes occurring in their cells of origin and are potential indicators in the early detection of cancers. This study aimed to determine whether certain exosomal miRNAs from tumor tissue can be used as noninvasive biomarkers for clear cell renal cell carcinoma (ccRCC). Based on ccRCC miRNA expression profiles and the literature, we selected six miRNAs (miR-210, miR-224, miR-452, miR-155, miR-21, and miR-34a) and analyzed their expression in tissues, sera, and serum exosomes through quantitative real-time polymerase chain reaction in hypoxia-induced (with CoCl2 ) renal cell lines. miR-210, miR-224, miR-452, miR-155, and miR-21 were upregulated in tumor tissues compared with normal tissues. Serum miR-210 and miR-155 levels were higher in patients with ccRCC than in healthy controls (HCs). Furthermore, only exosomal miR-210 was significantly upregulated in patients with ccRCC than in HCs. Moreover, receiver operating characteristic (ROC) curve analysis revealed an area under the ROC curve of 0.8779 (95% confidence interval, 0.7987-0.9571) and a sensitivity and specificity of 82.5% and 80.0%, respectively. Moreover, exosomal miR-210 was upregulated at an advanced stage, and Fuhrman grade and metastasis decreased significantly one month after surgery. Acute hypoxia exposure activates miR-210 and release of exosomes with upregulated miR-210 in both normal and tumor RCC cell lines and interferes with vacuole membrane protein 1 mRNA expression, especially in the metastatic ccRCC cell line. In conclusion, Serum exosomal miR-210 originating from tumor tissue has potential as a novel noninvasive biomarker for the detection and prognosis of ccRCC.

MicroRNA-21 as a predictor and prognostic factor for trastuzumab therapy in human epidermal growth factor receptor 2-positive metastatic breast cancer.

Breast cancer is the second most common cancer diagnosed worldwide. Human epidermal growth factor receptor 2 (HER2)-positive breast cancer represents about 20% to 30% of all breast cancers. Trastuzumab is used in the treatment of HER2-positive breast cancer. MicroRNA-21 (miR-21) is an oncomiR that acts by inhibiting many tumor-suppressor genes. We analyzed the relative expression levels of serum miR-21 in 20 HER2-positive metastatic breast cancer patients before and after 3 months of treatment with trastuzumab. miR-21 levels decreased with a high significant difference after trastuzumab therapy (P = 0.001). Although miR-21 expression levels were lower in responders than in nonresponders, the difference was not statistically significant ( P = 0.6). Our results demonstrated a significant negative correlation between its basal expression, expression levels after treatment, and time to progression ( P = 0.03 and 0.01, respectively). These results make miR-21 a potential prognostic factor for HER2-positive metastatic breast cancer patients. Additionally, it can be an interesting potential target in therapy using antisense oligonucleotides for miR-21.

Utility of Serum miR-122, Liver Enzymes, and Hepatic Histopathology in Response to Hepatotoxicants in Sprague-Dawley Rats.

More than 80,000 chemicals are in commercial use worldwide. Hepatic metabolism to toxic intermediates is often a key mechanism leading to tissue damage and organ dysfunction. Effective treatment requires prompt detection of hepatotoxicity, ideally with rapid, minimally invasive diagnostic assays. In this study, archetypal histologic features of chemically induced hepatic injury were compared with clinical chemistries (including liver enzymes) and serum concentrations of microRNA-122 (miR-122, the processed form miR-122-5p), a biomarker of liver injury. The hepatotoxicants 4,4'-methylenedianiline (4,4'-MDA), allyl alcohol (AA), or carbon tetrachloride (CCl4) were orally administered to male Sprague-Dawley rats for 1, 5, 14, or 28 days to induce liver damage. Formalin-fixed, paraffin-embedded liver sections were evaluated histologically for inflammation, fibrosis, necrosis, and lipid accumulation. Liver enzymes were measured in serum, and serum miR-122 concentrations were assessed by quantitative polymerase chain reaction (qPCR). Histologic features of hepatic injury dose-dependently increased in both severity and frequency. Increases in liver enzymes and bilirubin were more pronounced in response to AA or 4,4'-MDA than to CCl4 at early time points. Elevated serum miR-122 levels in animals administered CCl4, AA, or 4,4'-MDA were more strongly associated with degree of hepatic histopathology than with dosage. Given this sensitive expression pattern postexposure, liver-specific miR-122 may improve the diagnostic accuracy of early hepatic injury.

Serum miR-29a and miR-122 as Potential Biomarkers for Non-Alcoholic Fatty Liver Disease (NAFLD).

Non-Alcoholic Fatty Liver Disease (NAFLD) is an over accumulation of triglyceride in the liver without alcohol consumption. Its major cause is insulin resistance. Patients with NAFLD can develop liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) are non-coding RNAs that regulate post-transcriptional gene silencing. Previous research reported that miR-29 family (a, b and c) and miR-122 have an important role in regulating insulin resistance related to NAFLD. The purpose of this study was to investigate that miR-29 and miR-122 can be possible biomarkers for non-invasive diagnosis of NAFLD. Serum samples were collected from 58 NAFLD patients and 34 healthy controls. MiRNAs were extracted from serum by using microRNA purification kit followed by polyuridylation, reverse transcription and quantitative real-time PCR. Also, we analyzed the correlation between miR-29 and miR-122 and level of liver inflammation in NAFLD patients. We found that the serum miR-29a levels in NAFLD patients were significantly lower (P = 0.006) than the control group, while miR-29c levels were unchanged, and miR-29b levels were undetectable. However, we found that serum miR-122 levels in NAFLD patients were significantly higher (P < 0.001) than those found in the control group. For miR-29a, the area under curve (AUC) was 0.679 (P = 0.0065) with 60.87% sensitivity and 82.35% specificity. For miR-122, the AUC was 0.831 (P < 0.0001) with 75.00% sensitivity and 82.35% specificity. Interestingly, the levels of serum miR- 122 were significantly different between patients without steatohepatitis (NAS < 4) and steatohepatitis (NAS ≥ 4), indicating that the levels of miR-122 were related to the severity of NAFLD. The levels of miR-29a and miR-122 might be beneficial and compelling as possible biomarkers for non-invasive diagnosis of NAFLD.

Serum miR-126 level combined with multi- detector computed tomography in the preoperative prediction of lymph node metastasis of gastric cancer.

Predicting lymph node metastasis (LNM) accurately is vital to design optimal treatment strategies preoperatively for gastric cancer (GC) patients. However, conventional tumor biomarkers and imaging techniques are not sufficient to predict LNM before surgery. miR-126 has been reported to play important roles in tumor metastasis which may represent a novel tumor biomarker. To assess the utility of the combination of serum miR-126 and multi-detector computed tomography (MDCT) in predicting LNM preoperatively in GC. Quantitative real-time polymerase chain reaction was performed to examine the serum miR-126 expression levels in 338 GC patients. MDCT was also performed. The cut-off value of preoperative serum miR-126 level for LNM was determined by receiver characteristic curve (ROC) analysis. Logistic regression analysis was used to determine independent predictors for LNM. The serum miR-126 levels of GC patients with LNM were significantly lower compared with those without LNM (p< 0.05). In addition, the later the N stage was, the lower the serum miR-126 level was in GC patients (p< 0.05). With a cut-off value of 63.4, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value of serum miR-126 for predicating LNM were 83.2%, 79.0%, 81.9%, 90.4% and 66.4%, respectively. The combination of serum miR-126 level and MDCT increased the accuracy of MDCT prediction for LNM from 69.2% to 86.7%. Serum miR-126 was an independent predictor for LNM. These results indicate for the first time that the combination of serum miR-126 and MDCT is useful for the prediction of LNM in GC.

Astragaloside IV improves renal function and fibrosis via inhibition of miR-21-induced podocyte dedifferentiation and mesangial cell activation in diabetic mice.

BackgroundPodocyte dedifferentiation and mesangial cell (MC) activation play an important role in many glomerular diseases associated with fibrosis. MicroRNA-21 (miR-21) is closely linked to renal fibrosis, but it is unknown whether and how miR-21 promotes podocyte dedifferentiation and MC activation and whether astragaloside IV (AS-IV) improves renal function and fibrosis through the regulation of miR-21.Materials and methodsCultured MCs, primary mouse podocytes, and diabetic KK-Ay mice were treated with AS-IV. Cell transfection, Western blot, real-time PCR, immunofluorescence assay, immunohistochemical assay, and electronic microscopy were used to detect the markers of podocyte dedifferentiation and MC activation and to observe the renal morphology.ResultsOur data showed that miR-21 expression was increased and that AS-IV decreased miR-21 levels in cells, serum, and kidney. Overexpressed miR-21 promoted podocyte dedifferentiation and MC activation, and treatment with AS-IV reversed this effect. Furthermore, the overexpression of miR-21 activated the β-catenin pathway and the transforming growth factor (TGF)-β1/Smads pathway in the process of podocyte dedifferentiation and MC activation, which was abolished by AS-IV treatment. In addition, both the Wnt/β-catenin pathway inhibitor XAV-939 and the TGF-β1/Smads pathway inhibitor SB431542 reversed the effect of AS-IV. Furthermore, AS-IV improved renal function and fibrosis in diabetic KK-Ay mice.ConclusionOur results indicated that AS-IV ameliorates renal function and renal fibrosis by inhibiting miR-21 overexpression-induced podocyte dedifferentiation and MC activation in diabetic kidney disease. These findings pave way for future studies investigating AS-IV as a potential therapeutic agent in the management of glomerular diseases.

The Effect of Zinc Sulfate on miR-122, miR-34a, Atioxidants, Biochemical and Histopathological Parameters Following Hepatic Ischemia/Reperfusion Injury in Rats.

Liver ischemia-reperfusion (IR) injury is a situation which occurs in various conditions such as pringle maneuver and liver transplantation. The regulatory effect of zinc sulfate (ZnSO4) is an important trace element on several liver disorders well known, but its effects on microRNAS (miR-122 and miR-34a) have not been evaluated. The goal of this study was to identify the protective effects of ZnSO4 on IR-induced liver injury, in particular, microRNAS in rats. Thirty-two male Wistar rats were randomly assigned into four groups (eight each group): sham, IR, ZnSO4 pretreatment, and ZnSO4 + IR groups. In sham and ZnSO4 pretreatment groups, animals received normal saline (N/S, 2ml/kg) and ZnSO4 (5mg/kg) for 7 consecutive days intraperitoneally (ip), then only laparotomy was performed. In IR and ZnSO4 + IR groups, N/S and ZnSO4, respectively, were given with the same dose, time, and route, before induction of ischemia for 45min followed by reperfusion for 60min. Blood sample was taken for biochemical and microRNAs analysis. Tissue specimens also were obtained for the measurements of antioxidant activities and histopathological evaluations. Our results showed that ZnSO4 pretreatment ameliorated histopathological changes decreased the increased serum levels of liver enzymes, miR-122 and miR-34a, and enhanced the decreased activity of antioxidant enzymes following hepatic IR injury. The present study indicated that ZnSO4 had potential hepatoprotective action against IR-induced injury. Therefore, it has been suggested that it can be administered as an anti-miR before elective hepatic surgeries for prevention of this complication.

Circulating microRNA-122 levels are important predictor of hepatitis B virus surface antigen seroclearance.

It is currently unclear what impact serum microRNA-122 (miR-122) levels have on clearance of hepatitis B virus (HBV) surface antigen (HBsAg) in HBV-infected patients who had not received antiviral therapy. The current study evaluated the impact of serum miR-122 levels on HBsAg seroclearance in 367 consecutive HBV-infected patients who had not received antiviral therapy between their initial and last visit, and investigated the predictive factors of HBsAg seroclearance. Cumulative HBsAg seroclearance rates were 13.5%, 32.0%, and 37.4% after 10, 20, and 30 years, respectively. The yearly incidence of HBsAg seroclearance over the investigated 30-year period was 1.25%. A significant and strong correlation was observed between serum miR-122 and HBsAg levels. Moreover, there was a significant correlation between serum miR-122 levels and the levels of HBV DNA, hepatitis B e-antigen, and HBV core-related antigen. The HBsAg seroclearance rate in patients with a <1.0-fold change of serum miR-122 levels was significantly higher than in those with a ≥1.0-fold change. Multivariate analysis identified age (≥30 years), HBV DNA levels (<2.2 log U/mL), HBV genotype (non-C), and serum miR-122 levels (<1.0-fold change) as significant predictors of HBsAg seroclearance. Our results indicated that serum miR-122 level is an important predictor of HBsAg seroclearance in Japanese patients who do not receive antiviral therapy. Understanding the complexity of the interactions among various virus-related and host-related factors could potentially help in the design of new therapies that enhance HBsAg seroclearance.

Association of circulating microRNA-122 with presence and severity of atherosclerotic lesions.

ObjectiveMicroRNA (miR)-122 is highly expressed in the liver, where it has been implicated as a regulator of fatty-acid metabolism. A recent study reported that miR-122 plays a role in pathogenesis of atherosclerosis; however, whether it connects with severity of atherosclerotic lesion is still controversial. We therefore investigated the association between miR-122 expression and presence and severity of coronary atherosclerotic plaque.MethodsDuring January–November 2017, we included 300 patients with coronary heart disease (CHD) and 100 subjects as the control group. MiR-122 content was detected by quantitative real-time polymerase chain reaction. MiR-122 level was identified in all subjects, and the Spearman correlation between miR-122 and severity of atherosclerosis was analyzed.ResultsPatients with CHD had higher miR-122 expression than in control group (2.61, 0.91–8.86 vs. 1.62, 0.71–3.45, p < 0.001). Gensini score was significantly associated with miR-122 expression (r = 0.7964, p < 0.001). The odds ratio of miR-122 solely was 0.12 (95% CI [0.05–0.43]) and factors such as cholesterol, triglyceride together with miR-122 level were closely associated with atherosclerosis (all p < 0.001).ConclusionsThe serum level of miR-122 may be used to differentiate between mild and severe coronary atherosclerotic lesion. Use of this marker might allow non-invasive diagnosis the degree of coronary atherosclerosis.

Serum miRNA-122 is an independent biomarker of survival in patients with primary sclerosing cholangitis.

The disease course of primary sclerosing cholangitis (PSC) is variable and difficult to predict. MicroRNA-122 (miR-122) is associated with various liver diseases. We investigated the value of miR-122 as a biomarker for the disease course of PSC. We determined serum miR-122 levels in a long-term, prospective cohort of 114 PSC patients and a second validation cohort. Based on miR-122 levels, PSC patients were assigned to low or high level miR-122 groups. Kaplan-Meier analysis showed significantly impaired actuarial transplant-free survival for PSC patients in the low miR-122 group (mean: 46.1 +/- 4.1 months; 95% confidence intervals [CI]: 38.1-54.2) compared to the high miR-122 group (mean: 95.2 +/- 7.9 months; 95% CI: 79.5-110.8; p = 0.034). Using a multivariate Cox's proportional hazards model approach, Mayo-Risk score (odds ratio [OR]: 1.47; 95% CI: 1.13‒1.92; p = 0.004), the presence of dominant strictures (OR: 2.62; 95% CI: 1.00‒5.55; p = 0.004), and serum miR-122 levels (OR: 1.19; 95% CI: 1.00‒1.43; p = 0.045) were independent risk factors associated with reduced actuarial transplant-free survival. We were able to confirm this finding in a second, independent cohort of PSC patients (low miR-122 group: mean survival: 13.1 +/- 5.2 months; 95% CI: 2.8-23.4; high miR-122 group: mean: 28.62 +/- 4.2 months; 95% CI: 20.3-37.0; p = 0.018). We identified miR-122 as a novel, independent prognostic biomarker associated with improved survival in PSC patients. It is unknown whether exogenous miR-122 might influence the disease course of PSC patients. .

Clinical application value of combined detection of serum miR-378 and miR-21 in gastric cancer

Objective: To investigate the clinical value of combined detection of serum miR-378 and miR-21 in gastric cancer (GC). Methods: Eighty-seven patients with GC and 78 patients with colorectal cancer(CRC) from National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences were selected, 83 individuals undergoing healthy physical examination were selected as the healthy controls. The levels of serum miR-378 and miR-21 were detected by quantitative real-time PCR (RT-qPCR) (result data were transformed as log2 for analysis). Results: Relative expression levels of miR-378 in the serum were -1.24, -3.25 and -2.73 in healthy controls, GC and CRC patients, respectively. Compared with the healthy controls, the levels of serum miR-378 were significantly decreased in GC and CRC patients (both P<0.05). Relative expression levels of miR-21 in the serum were 0.11, 2.34 and 2.47 in healthy controls, GC and CRC patients, respectively. Compared with the healthy controls, the levels of serum miR-21 were significantly up-regulated in GC and CRC patients (both P<0.05). Moreover, the serum level of miR-378 in GC patients was inversely associated with tumor clinical stage (P<0.05). However, the level of miR-21 showed no significant differences among patients with different clinical and pathological characteristics (all P>0.05). The area under the receiver operating characteristic curve (AUC), sensitivity and specificity of miRNA-378 to diagnose GC was 0.770, 82.0% and 66.0%, respectively, and were 0.900, 85.0%, and 88.0% of miR-21, respectively. The AUC, sensitivity and specificity of combined detection of serum miR-378 and miR-21 to diagnose GC were 0.930, 92.0% and 87.0%, respectively, while the AUC of combined detection of serum CEA and CA-199 was 0.767, the AUC of combined all of the four factors was 0.946. Conclusion: The combined detection of serum miR-378 and miR-21 have a certain effect on diagnosis of GC.

MicroRNA profiles in serum samples from patients with stable cirrhosis and miRNA-21 as a predictor of transplant-free survival

MicroRNAs (miRNAs) have remarkable potential as diagnostic and prognostic markers because of their roles in disease pathogenesis. miRNAs can be released into the bloodstream, where they are sufficiently stable to be detected noninvasively. Here, we prospectively evaluated serum levels of miR-21, miR-34a, miR-122, miR-181b, and miR-885-5p in patients with stable cirrhosis. Total RNA was extracted from the sera of patients with cirrhosis and healthy individuals, and the expression levels of the target miRNAs were analyzed by reverse transcription-quantitative polymerase chain reaction. Serum miRNAs levels were correlated with liver function parameters, etiology, and complications of cirrhosis. Circulating miR-34a, miR-122, and miR-885-5p levels were higher in patients with cirrhosis than in healthy individuals. These miRNAs were positively correlated with alanine aminotransferase and aspartate aminotransferase levels, and the relative expression levels were higher in hepatitis C virus-infected patients and lower in patients with Child-Pugh C cirrhosis. miR-122 and miR-885-5p levels were also positively correlated with γ-glutamyl transpeptidase concentrations. miR-21 was associated with transplant-free survival in univariate Cox regression analysis and remained independently associated with survival after adjustment for age, Child-Pugh classification, Model for End-stage Liver Disease score, and history of previous decompensation in multivariate Cox regression analysis. These data suggested that miR-34a, miR-122, and miR-885-5p levels may be more related to the inflammatory process and ongoing hepatocyte damage in patients with cirrhosis. Moreover, miR-21 levels were independently associated with shorter transplant-free survival and may be used as a prognostic tool in outpatients with stable cirrhosis.

Circulating serum oncologic miRNA in pediatric juvenile pilocytic astrocytoma patients predicts mural nodule volume.

Juvenile pilocytic astrocytomas represent the largest group of pediatric brain tumors. The ideal management for these tumors is early, total surgical resection. To detect and track treatment response, a screening tool is needed to identify patients for surgical evaluation and assess the quality of treatment. The identification of aberrant miRNA profiles in the sera of juvenile pilocytic astrocytoma patients could provide such a screening tool. The authors reviewed the serum profiles of 84 oncologically relevant miRNAs in pediatric juvenile pilocytic astrocytoma patients via qPCR screening. miR-21, miR-15b, miR-23a, and miR-146b were significantly elevated in the sera of JPA patients as compared to non-oncologic controls, oncologic controls, and post-JPA resection samples (p < 0.001, 0.022, 0.034, 0.044). miR-21 had the highest AUC on ROC analysis (AUC > 0.99, sensitivity 75%, specificity 100%). All four miRNAs also correlated well with tumor mural nodule size, though they only poorly correlated with total tumor size, including cystic components (Spearman's R2: miR-21 91.7 vs 6.9%, miR-15b 86.3 vs 23.1%, miR-23a 85.8 vs 23.0%, miR-146b 59.8 vs 11.9%). In this small pilot study, pediatric juvenile pilocytic astrocytoma patients had significant elevations in serum miR-21, miR-15b, miR-23a, and miR-146b levels that do not appear to be driven by hydrocephalus or local distortion of the intracranial contents. These alterations correlate with solid tumor component volume and reverse with complete tumor resection, suggesting that this serum miRNA profile may delineate biomarkers for screening and tracking juvenile pilocytic astrocytoma patients. Additional studies, with a larger cohort, are needed to verify these results.

Circulating MicroRNA-21 Correlates With Left Atrial Low-Voltage Areas and Is Associated With Procedure Outcome in Patients Undergoing Atrial Fibrillation Ablation.

Background:Atrial fibrosis is a hallmark of arrhythmogenic structural remodeling in patients with persistent atrial fibrillation (AF) and is negatively correlated with procedure outcome in patients undergoing ablation. However, noninvasive methods to determine the extent of atrial fibrosis are limited. Here, we used microRNA (miRNA) expression analysis to detect markers of left atrial low-voltage areas (LVAs) in patients with persistent AF undergoing catheter ablation.Methods:We performed 3-dimensional voltage mapping in 102 patients (average age 62.1±13.1 years, CHA2DS2-VASc score of 2.3±1.6, LA size 41.5±5.7 mm) undergoing ablation for persistent AF and determined the extent of left atrial low-voltage. LVAs were defined if bipolar electrogram amplitudes were <0.5 mV during sinus rhythm. Before ablation, we obtained a blood sample, isolated miRNAs, and profiled them on a miRCURY LNA Universal RT microRNA PCR Human panel.Results:Sixty-nine miRNAs were identified in all samples, with an average of 123 miRNAs detectable per sample. We found that the serum concentration of miR-21, a miRNA that has been previously linked to cardiac fibrosis development, was strongly associated with the extent of LVAs determined by voltage mapping. We could confirm that LVAs were negatively correlated with ablation success in a 1-year follow-up. In addition, miR-21 serum levels were associated with AF-free survival after catheter ablation.Conclusions:Circulating miR-21 correlates with left atrial LVAs and is associated with procedure outcome in patients with persistent AF undergoing ablation.

Clinical evaluation of 4 types of microRNA in serum as biomarkers of esophageal squamous cell carcinoma.

To the best of our knowledge, there is currently no specific biomarker for esophageal cancer used in clinical practice. However, studies consider that microRNAs (miRNAs/miRs) could have useful implications in clinical practice. The present study aimed to investigate the feasibility of using serum microRNAs as biomarkers for esophageal squamous cell carcinoma (ESCC). Using reverse transcription-quantitative polymerase chain reaction, the expression levels of serum miR-21, miR-25, miR-145 and miR-203 were detected in 31 untreated patients with ESCC (EC-UT), 35 inactive period patients with ESCC following treatment (EC-T), 33 patients with esophageal benign disease (benign) and 32 healthy donors (healthy). Furthermore, the ability of these microRNAs to function as biomarkers of ESCC alone and in combination were investigated. The expression levels of serum miR-21, miR-25 and miR-145 in EC-UT were significantly higher than in the other groups (P<0.001). High sensitivity and specificity were shown when miRNAs were used as biomarkers for ESCC, particularly miR-21 and the combination of miR-21 with miR-145. Comparing EC-UT with healthy, benign and EC-T groups, and a combined group (3 groups set as 1 negative control), the sensitivity and specificity of miR-21 were 71.0 and 96.9, 74.2 and 87.9, 77.4 and 82.9, and 74.2 and 88.0%, respectively. The combined sensitivity and specificity of miR-21 and miR-145 were 71.0 and 96.9, 90.9 and 72.7, 97.1 and 82.9, and 80.6 and 80.0%, respectively. In conclusion, 3 types of miRNA (miR-21, miR-25 and miR-145) in serum could serve as potential biomarkers for ESCC. Furthermore, the expression level of miR-145 in serum was upregulated, compared with the downregulation reported in previous studies in ESCC tissues and cells.

Down-regulated serum miR-126 is associated with aggressive progression and poor prognosis of gastric cancer.

miR-126 functions as a tumor suppressor in gastric cancer (GC), however, the clinical significance of serum miR-126 in GC remains unclear. To investigate the associations of serum miR-126 level with the clinicopathological characteristics and prognosis of GC patients. Quantitative real-time polymerase chain reaction was performed to examine the expression levels of miR-126 in 338 GC patients' tissues and sera, and 50 healthy controls' sera. The associations of serum miR-126 with clinicopathological characteristics and clinical outcome were evaluated. Compared with the matched adjacent non-tumor tissues and normal sera, miR-126 expression was significantly down-regulated in both tumor tissues and sera of GC patients. Importantly, there was a positive correlation between tissue and serum levels of miR-126 in GC patients. A reduced serum miR-126 level statistically correlated with aggressive clinicopathological characteristics, such as larger tumor size, deeper local invasion, more lymph node metastasis, advanced TNM stage, and poorer prognosis. Notably, multivariate analysis identified reduced serum miR-126 level as an independent predictor for the unfavorable prognosis of GC. These results indicate for the first time that serum miR-126 may serve as a novel prognostic biomarker in GC.

Effect of blood purification on serum miR-126 and VEGF levels in the process of atherosclerosis in uremic patients under maintenance hemodialysis

This study aims to study the influence of different blood purification approaches on the expression of miR-126 and VEGF serum levels in the development of atherosclerosis in uremic patients under maintenance hemodialysis (MHD). A total of 207 MHD patients with uremia were divided into HD (hemodialysis, n = 60), HDF (hemodiafiltration, n = 72), and HD + HP (hemodialysis + hemoperfusion, n = 75) groups based on different purification approaches. Eighty individuals who underwent physical examinations during the same period constituted the healthy controls. The serum levels of miR-126 and VEGF were examined by qRT-PCR and ELISA both before and after treatment, and the intima media thickness (IMT) value and plaque area were evaluated by color Doppler ultrasound. The serum miR-126 level was down-regulated in MHD patients compared with healthy controls, and this was negatively linked to VEGF. The post-treatment expression level of serum miR-126 in the HDF and HD + HP groups was remarkably increased, but VEGF was decreased in MHD patients, and especially significantly in the HDF group. In addition, IMT and plaque area were obviously improved in the HD group after treatment. Pearson correlation analysis showed a negative correlation of miR-126 with IMT and plaque area, but a positive association between VEGF and IMT and plaque area. miR-126 and VEGF are expected to become a valuable biomarker for monitoring the progression of atherosclerosis in uremic patients undergoing MHD.

Serum Levels of miR-155, miR-326, and miR-133b as Early Diagnostic Biomarkers for the Detection of Human Acute Heart Allograft Rejection in Comparison with Serum Cardiac Troponin T.

Acute heart allograft rejection occurs as a result of antibody-mediated rejection that presents during the first month after transplantation. Finding a non-invasive biomarker is essential for diagnosis of heart allograft rejection. In this research, we intended to compare expression levels of several microRNAs across cardiac troponin T levels between rejected patients (who died before one month following transplantation), non-rejected patients (who survived for at least one month after transplantation), and non-transplanted patients (CABG surgery patients). Serum levels of miR-155, miR-326, and miR-133b were evaluated by the q-RT-PCR method. Furthermore, cardiac troponin T levels were measured by a highly sensitive electrochemiluminescence assay. Finally, the data were analyzed by independent sample t-test using SPSS 21® computer software.Results: It was observed that miR-326 and miR-155 expression levels increased after 24h and 72h of surgery in rejected patients compared with the two other groups, but these increases were not statistically significant. Moreover, the decrease in miR-133b expression level was non-significant after transplantation in the rejected group compared with the non-rejected group. However, cTnT levels in rejected patients increased significantly compared with the other groups (P < .05). After ROC curve analysis, the cTnT marker with the most area under the curve (AUC = 1.00, 95% confidence interval, 1.00 to 1.00; P = .006), had the best discriminatory power, and among microRNAs, miR-326 had the largest area under curve (AUC = 0.81), and consequently the highest discriminatory power. We demonstrated that troponin T can be a more efficient biomarker than miRNAs for early prediction of human death caused by acute heart rejection, and the ROC curves analysis verified this finding.