Serum miR-21 Research Articles

Dysregulation of miR-210 is involved in the development of diabetic retinopathy and serves a regulatory role in retinal vascular endothelial cell proliferation

BackgroundDiabetic retinopathy is a common complication of diabetes mellitus (DM). The purpose of this study was to investigate the expression and clinical significance of miR-210 in DR patients and explore the regulatory effect of miR-210 on vascular endothelial cell function under high-glucose condition.MethodsQuantitative real-time PCR was used to estimate miR-210 expression. A receiver operating characteristics curve (ROC) was plotted to evaluate the diagnostic value of miR-210. Human umbilical vein endothelial cells (HUVECs) were used and treated with high glucose (30 mM), and the cell proliferation was assessed by MTT assay.ResultsSerum expression of miR-210 was upregulated in DR patients compared with DM without DR patients and healthy controls. The expression of miR-210 in proliferative DR (PDR) patients was higher than non-proliferative DR (NPDR) patients. The increased serum miR-210 could be used to distinguish DR cases from healthy individuals and also simple DM patients, and can screen PDR cases from NPDR cases. The overexpression of miR-210 promoted HUVEC proliferation, while the knockdown of miR-210 resulted in the opposite effect under a high-glucose condition.ConclusionThe data of this study demonstrated that serum increased miR-210 serves as a diagnostic biomarker in DR patients and may have the ability to predict DR development and severity. The regulatory effect of miR-210 on vascular endothelial cell proliferation under high-glucose condition, indicating its therapeutic potential in the treatment of diabetic vascular diseases.

MIR1246 in body fluids as a biomarker for pancreatic cancer

Pancreatic cancer is an aggressive tumor associated with poor survival, and early detection is important to improve patient outcomes. In the present study, we examined MIR1246 expression as a biomarker of pancreatic cancer. Total RNA was extracted from serum, urine and saliva samples from healthy subjects (n = 30) and patients with pancreatic cancer (n = 41, stage 0–IV). The MIR1246 level in each fluid was analyzed by quantitative reverse transcription-polymerase chain reaction. Significantly higher MIR1246 expression in serum and urine was observed in patients with cancer than in healthy controls. A significant positive correlation was found between serum and urine MIR1246 expression (r = 0.34). Receiver operating characteristic curves were constructed for MIR1246 in all three body fluids. The area under the curve for serum MIR1246 was 0.87 (sensitivity, 92.3%; specificity, 73.3%), and that for urine MIR1246 was 0.90 (sensitivity, 90.2%; specificity, 83.3%). With a cut-off of the control group’s mean plus twice the standard deviation, the sensitivities of MIR1246 in serum and urine for pancreatic cancer were 60.9 and 58.5%, respectively. Combining both serum and urine MIR1246 expression yielded a sensitivity of 85%. These results indicate that MIR246 may be a useful diagnostic biomarker for pancreatic cancer.

Thymoquinone potentiates miR-16 and miR-375 expressions in hepatocellular carcinoma

AimsMicroRNAs (miRNAs) are non-coding RNAs that control post-transcriptional gene expression. Recently, miRNAs were confirmed to be promising biomarkers for different pathological conditions. This study assessed the role of serum miR-16 and miR-375 in HCC development in chronic liver disease patients such as cirrhosis. Moreover, miR-16 and miR-375 levels were estimated in HCC cell lines (HepG2 and Huh7) after treatment with doxorubicin (DOX), thymoquinone (TQ) and their combination. Main methodsSerum miR-16 and miR-375 were analyzed in 30 HCC patients, 20 cirrhosis patients and 10 healthy volunteers using RT-PCR. Moreover, HepG2 and Huh7 cells were incubated with DOX, TQ or TQ/DOX combination for 24 h and the levels of miR-16, miR-375 and gene expression of anti-apoptotic protein BCL-2 were determined in cell lysates using RT- PCR. Moreover, the ability of DOX, TQ and TQ/DOX combination to induce apoptosis were analyzed by measuring caspase-3 expression using ELISA method. Key findingsSerum miR-16 and miR-375 levels were significantly decreased in HCC patients as compared to cirrhosis and healthy control group. Also, combined use of serum miR-16 and miR-375 showed a better predictive ability than each alone. Moreover, the expression level of miR-16 and miR-375 in HepG2 and Huh7 cells increased significantly after treatment with DOX and TQ. Also, TQ/DOX combination improved apoptosis by increasing caspase-3 expression and decreasing of BCL-2 expression. SignificanceThis study proved that the combined use of serum miR-16 and miR-375 was better than each alone for HCC detection. Moreover, TQ induced apoptosis and upregulatedmiR-16 and miR-375 expression in HCC cells that may explain its anticancer activity.

MiR-155 facilitates calcium oxalate crystal-induced HK-2 cell injury via targeting PI3K associated autophagy

Nephrolithiasis is one of the most common and highly recurrent diseases worldwide. Accumulating evidence revealed the elevated miR-155 levels both in serum and urine of nephrolithiasis patients. The aim of our research was to explore the role of miR-155 in CaOx-induced apoptosis in HK-2 cells. The expression levels of miR-155 in serum and renal tissues were quantified in 20 patients with nephrolithiasis using qRT-PCR assay. ELISA was performed to determine urinary levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-alpha (TNF-α). Renal tubular cell model of CaOx nephrolithiasis was established to investigate the role and molelular mechanism of miR-155. Cell viability and apoptosis were assessed by MTT and flow cytometry, respectively. Immunofluoresent staining of LC3 autophagosome and western blotting were performed to evaluate the autophagic activity. Luciferase reporter assay was employed to verify the interaction between miR-155 and PI3KCA/Rheb. PI3K/Akt/mTOR signaling was further examined by western blotting. Serum and renal levels of miR-155 and inflammatory factors were significantly elevated in nephrolithiasis patients than in controls. CaOx treatment caused up-regulation of miR-155 and induced autophagy in renal tubular epithelial cells, while silencing miR-155 or inhibition of autophagy by 3-metheladenine (3-MA) ameliorated CaOx crystal-induced cell injury. PI3KCA and Rheb was identified as downstream targets of miR-155. Moreover, miR-155 activates autophagy and promotes cell injury through repressing PI3K/Akt/mTOR signaling pathway. Taken together, these findings demonstrated that miR-155 facilitates CaOx crystal-induced renal tubular epithelial cell injury via PI3K/Akt/mTOR-mediated autophagy, providing therapeutic targets for ameliorating cellular damage by CaOx crystals.

MiR-21 and Pellino-1 Expression Profiling in Autoimmune Premature Ovarian Insufficiency.

Background Premature ovarian insufficiency (POI) represents the hypergonadotropic hypoestrogenic symptoms that result in the loss of ovarian follicles. 5-30% POI cases are suggested to be involved in autoimmune etiology. MicroRNA-21 (miR-21) plays a vital role in ovarian folliculogenesis via regulating and interacting with multiple target genes. Here, we conduct the target prediction of miR-21, identify the expression and correlation of miR-21 and its putative target Pellino-1 (Peli1), and confirm their relationship with clinical characteristics in autoimmune POI. Methods Bioinformatic analysis was conducted to screen the miR-21 putative target gene. Autoimmune POI mouse models were established by ZP3 immunization. Serum miR-21, Peli1 mRNA of peripheral blood mononuclear cells (PBMCs) and regulatory T cells (Tregs), general status, spleen Tregs ratio, inflammatory factors, ovarian endocrine function, and ovarian structure were evaluated. For autoimmune POI patients, serum miR-21, PBMCs Peli1 mRNA levels, general data, immune parameters, hormone levels, and ultrasound examinations were obtained. The correlations of miR-21 with Peli1 and clinical characteristics in patients were analyzed. Results Peli1 was selected based on four microRNA prediction databases and literature retrieval. In mouse models, serum miR-21 level, PBMCs and Tregs Peli1 mRNA, and spleen Tregs ratio were 0.61 ± 0.09, 0.12 ± 0.12, 0.27±0.23 and 4.82 ± 0.58, respectively, lower than those in the control group. In patients, miR-21 level (0.60 ± 0.14) and Peli1 mRNA (0.30 ± 0.14) were lower than those in the control group (1.01 ± 0.07 and 1.63 ± 0.54); miR-21 was positively related with Peli1, AMH, E2, the size of the uterus, and ovarian volume and negatively related with FSH, LH, and the number of positive immune parameters (AOAb, EMAb, ACL, ANA, ds-DNA, ACA, IgG, IgA, IgM, IgE, C3, and C4). Conclusions Low expressions of miR-21 and Peli1 were detected in autoimmune POI mice and patients. Positive correlation between miR-21 and Peli1 was observed in autoimmune POI patients, suggesting that miR-21 and Peli1 might be associated with the pathogenesis of autoimmune POI.

Serum level of miR-126 in patients with hypertensive intracerebral hemorrhage and its clinical significance

Objective To investigate the serum level of miR-126 in patients with hypertensive intracerebral hemorrhage and to elucidate its clinical significance in hypertensive cerebral hemorrhage. Methods From January 2015 to December 2018, 60 patients with hypertensive cerebral hemorrhage were selected as observation group, and 60 healthy subjects were selected as control group in the People's Hospital of Lin'an Affiliated to Hangzhou Medical College.The serum levels of miR-126 were determined by reverse transcription-polymerase chain reaction (RT-PCR). The serum levels of C-reactive protein (CRP), tumor necrosis factor-ɑ (TNF-ɑ) and nuclear factor kappa B (NF-κB) were measured by enzyme-linked immunosorbent assay (ELISA). Results The serum level of miR-126 in the observation group was lower than that in the control group [(0.46±0.11) vs.(1.00±0.13), t=24.562, P<0.05], and the serum levels of CRP, TNF-ɑ and NF-κB were higher than those in the control group[(8.74±0.69)mg/L vs.(3.98±0.61)mg/L, (62.43±8.26)μg/L vs.(31.28±6.54)μg/L, (19.73±1.02)μmol/L vs.(4.92±0.87)μmol/L, t=40.034, 22.902, 85.570, all P<0.05]. There were statistically significant differences in serum miR-126, CRP, TNF-ɑ, NF-κB levels among patients with different severity of hypertensive intracerebral hemorrhage[(0.57±0.09) vs.(0.44±0.12) vs.(0.36±0.11), (6.91±0.72)mg/L vs.(8.63±0.67)mg/L vs.(9.14±0.75)mg/L, (53.16±8.19)μg/L vs.(62.57±8.33)μg/L vs.(70.38±8.09)μg/L, (12.49±0.97)μmol/L vs.(19.58±1.11)μmol/L vs.(25.64±1.05)μmol/L, F=14.433, 41.379, 17.796, 623.893, all P<0.05], with the severity increased, the serum miR-126 level decreased, serum CRP, TNF-ɑ and NF-κB levels increased.The serum miR-126 level in patients with hypertensive cerebral hemorrhage of the poor prognosis group was lower than that of the good prognosis group [(0.53±0.10) vs.(0.38±0.12), t=5.279, P<0.05], and the serum levels of CRP, TNF-ɑ and NF-κB in the poor prognosis group were higher than those in the good prognosis group[(7.85±0.64)mg/L vs.(9.16±0.73)mg/L, (51.07±8.32)μg/L vs.(73.26±8.17)μg/L, (14.73±1.08)μmol/L vs.(26.52±0.99)μmol/L, t=7.392, 10.317, 43.424, all P<0.05]. The area of brain edema in patients with hypertensive intracerebral hemorrhage was negatively correlated with serum miR-126 (r=-0.623, P<0.05), and positively correlated with serum CRP, TNF-ɑ and NF-κB (r=0.581, 0.618, 0.642, all P<0.05). The serum miR-126 level was negatively correlated with CRP, TNF-ɑ and NF-κB in patients with hypertensive intracerebral hemorrhage (r=-0.593, -0.624, -0.618, all P<0.05). Conclusion The serum level of miR-126 is reduced in patients with hypertensive intracerebral hemorrhage, which may participate in the pathogenesis of hypertensive cerebral hemorrhage by participating in inflammatory reaction.The detection of serum miR-126 level has great value in evaluation of the severity and prognosis of hypertensive cerebral hemorrhage. Key words: Intracranial hemorrhage, hypertensive; MicroRNAs; C-reactive protein; Tumor necrosis factor-alpha; Nuclear transcription factor κB

Combined Value of Serum miR-124, TNF-α and IL-1β for Vulnerable Carotid Plaque in Acute Cerebral Infarction.

To analyse correlation between serum miR-124, TNF-α and IL-1β levels and carotid vulnerable spots in acute cerebral infarction (ACI) patients, and explore the value of above biomarkers in diagnosing carotid artery plaques in ACI patients. Descriptive study. Department of Neurology, Affiliated Hospital of Shandong Medical College, China, from January 2018 to November 2019. A total of 160 ACI patients with carotid atherosclerosis were divided into 73 cases of stable plaque group and 87 cases of vulnerable plaque group based on the results of carotid ultrasound. Receiver operating characteristic (ROC) curve was used to evaluate efficacy of serum miR-124, TNF-α and IL-1β used alone or in combination to diagnose carotid vulnerable plaques in ACI. Serum miR-124 relative expression, TNF-α and IL-1β levels in vulnerable plaque group were higher than those in stable plaque group (all p<0.001). Serum miR-124 in vulnerable plaque group was positively correlated with TNF-α and IL-1β levels (r = 0.976, p<0.001; and r = 0.974, p <0.001). AUC for miR-124, TNF-α, and IL-1β combined in diagnosis of vulnerable carotid plaques was 0.853 (95% CI: 0.790-0.915), with a sensitivity of 82.80%, and a specificity of 78.90%. The AUC diagnosed by miR-124, TNF-α, and IL-1β was greater than all the AUCs diagnosed by three indicators alone. Serum miR-124, TNF-α and IL-1β can be used as indicators for early auxiliary diagnosis of vulnerable carotid plaques in patients with ACI, and combination of the three has the best diagnostic efficacy. Key Words: Acute cerebral infarction (ACI) Serum, miR-124, TNF-α, IL-1β, Vulnerable carotid plaque.

Intracranial Self-Stimulation Modulates Levels of SIRT1 Protein and Neural Plasticity-Related microRNAs.

Deep brain stimulation (DBS) of reward system brain areas, such as the medial forebrain bundle (MFB), by means of intracranial self-stimulation (ICSS), facilitates learning and memory in rodents. MFB-ICSS has been found capable of modifying different plasticity-related proteins, but its underlying molecular mechanisms require further elucidation. MicroRNAs (miRNAs) and the longevity-associated SIRT1 protein have emerged as important regulatory molecules implicated in neural plasticity. Thus, we aimed to analyze the effects of MFB-ICSS on miRNAs expression and SIRT1 protein levels in hippocampal subfields and serum. We used OpenArray to select miRNA candidates differentially expressed in the dentate gyrus (DG) of ICSS-treated (3 sessions, 45' session/day) and sham rats. We further analyzed the expression of these miRNAs, together with candidates selected after bibliographic screening (miR-132-3p, miR-134-5p, miR-146a-5p, miR-181c-5p) in DG, CA1, and CA3, as well as in serum, by qRT-PCR. We also assessed tissue and serum SIRT1 protein levels by Western Blot and ELISA, respectively. Expression of miR-132-3p, miR-181c-5p, miR-495-3p, and SIRT1 protein was upregulated in DG of ICSS rats (P < 0.05). None of the analyzed molecules was regulated in CA3, while miR-132-3p was also increased in CA1 (P = 0.011) and serum (P = 0.048). This work shows for the first time that a DBS procedure, specifically MFB-ICSS, modulates the levels of plasticity-related miRNAs and SIRT1 in specific hippocampal subfields. The mechanistic role of these molecules could be key to the improvement of memory by MFB-ICSS. Moreover, regarding the proposed clinical applicability of DBS, serum miR-132 is suggested as a potential treatment biomarker.

Circulating MicroRNA-122 for the Diagnosis of Hepatocellular Carcinoma: A Meta-Analysis.

Background Circulating microRNA-122 (miR-122) has been recognized as a marker of hepatocellular carcinoma (HCC). The current meta-analysis was performed to quantitatively evaluate the diagnostic performance of circulating miR-122 for HCC. Methods Related studies that evaluated the diagnostic performance of circulating miR-122 determined from pathophysiological examination for HCC were obtained by systematic searches of the PubMed and Embase databases. A randomized fixed effects model was applied according to the heterogeneity among studies. The pooled sensitivity, specificity, and area under the summary receiver operating characteristic curve (AUC) were calculated to evaluate the diagnostic accuracy. Publication bias was detected by Deeks' funnel plot asymmetry test. Results Thirteen studies providing data for 920 HCC patients and 1217 controls were included in the meta-analysis. The pooled sensitivities, specificities, and AUCs of serum miR-122 were 0.76, 0.75, and 0.82, respectively, for discriminating HCC patients from overall controls; 0.85, 0.83, and 0.91, respectively, for discriminating HCC patients from healthy controls; 0.79, 0.82, and 0.87, respectively, for discriminating HCC from HBV or HCV infection; and 0.65, 0.75, and 0.74, respectively, for discriminating HCC from liver cirrhosis or dysplastic nodule formation. No significant publication bias was detected. Conclusions Serum miR-122 confers moderate efficacy for discriminating HCC patients from healthy controls or patients with HBV or HCV infection, but not for discriminating HCC patients from those with liver cirrhosis or dysplastic nodule formation.

Circulating microRNAs in Response to Exercise Training in Healthy Adults.

Circulating microRNAs (miRNAs, miRs) have great potential as cardiac biomarkers and they are also being explored for their roles in intercellular communication and gene expression regulation. The analysis of circulating miRNAs in response to exercise would provide a deeper understanding of the molecular response to physical activity and valuable information for clinical practice. Here, eight male college students were recruited to participate in cardiopulmonary exercise testing (CPET) and 1 h acute exercise training (AET). Blood samples were collected and serum miRNAs involved in angiogenesis, inflammation and enriched in muscle and/or cardiac tissues were analyzed before and after cardiopulmonary exercise and acute exercise. The miRNAs we detected were miR-1, miR-20a, miR-21, miR-126, miR-133a, miR-133b, miR-146, miR155, miR-208a, miR-208b, miR-210, miR-221, miR-222, miR-328, miR-378, miR-499, and miR-940. We found that serum miR-20a was decreased significantly after CPET and serum miR-21 was increased after AET. In addition, no robust correlation was identified between the changes of these miRNAs and makers of cardiac function and exercise capacity, which indicates a distinct adaptation of these miRNAs to exercise. Future studies are highly needed to define the potential use of these circulating miRNAs as useful biomarkers of exercise training, and disclose the biological function of circulating miRNAs as physiological mediators of exercise-induced cardiovascular adaptation.

Circulating miRNA-21 as a diagnostic biomarker in elderly patients with type 2 cardiorenal syndrome

Circulating miRNAs have attracted attention as serum biomarkers for several diseases. In this study, we aimed to evaluate the diagnostic value of circulating miRNA-21 (miR-21) as a novel biomarker for elderly patients with type 2 cardiorenal syndrome (CRS-2). A total of 157 elderly patients with chronic heart failure (CHF) were recruited for the study. According to an estimated glomerular filtration rate (eGFR) cut-off of 60 ml/min/1.73 m2, 84 patients (53.5%) and 73 patients (46.5%) were assigned to the CRS group and the CHF group, respectively. Expression levels of serum miR-21 and biomarkers for CRS, such as kidney injury factor-1 (KIM-1), neutrophil gelatinase-related apolipoprotein (NGAL), cystatin C (Cys C), amino-terminal pro-B-type natriuretic peptide (NT-proBNP), N-acetyl-κ-D-glucosaminidase (NAG), and heart-type fatty acid–binding protein (H-FABP), were detected. Serum miR-21, KIM-1, NGAL, Cys C, NT-proBNP and H-FABP levels were significantly higher in the CRS group than in the CHF group (P < 0.01), whereas NAG expression was not significantly different between the two groups (P > 0.05). Cys C, H-FABP and eGFR correlated significantly with miR-21 expression, but correlations with miR-21 were not significant for NT-proBNP, NGAL, NAG and KIM-1. Moreover, multivariate logistic regression found that serum miR-21, increased serum Cys C, serum KIM-1, hyperlipidaemia and ejection fraction (EF) were independent influencing factors for CRS (P < 0.05). The AUC of miR-21 based on the receiver operating characteristic (ROC) curve was 0.749, with a sensitivity of 55.95% and a specificity of 84.93%. Furthermore, combining miR-21 with Cys C enhanced the AUC to 0.902, with a sensitivity of 88.1% and a specificity of 83.6% (P < 0.001). Our findings suggest that circulating miR-21 has medium diagnostic value in CRS-2. The combined assessment of miR-21 and Cys C has good clinical value in elderly patients with CRS-2.

Correlation between miR-223 and IL-35 and their regulatory effect in children with allergic rhinitis

The relationship between microRNA (miR) and immune activity in allergic rhinitis (AR) remains unclear. 37 children with AR and 30 healthy children were enrolled to study the correlation of miR-223 and IL-35. There was a significant inverse correlation between plasma levels of IL-35 and serum eosinophil cationic protein (ECP) levels and eosinophils counts, while there was a positive correlation between serum miR-223 level and ECP levels and eosinophils counts. Besides, the serum levels of IL-35 or miR-223 were found to be negatively or positively correlated with TNSS respectively. The serum level of miR-223 was increased, while IL-35 level was decreased. Moreover, the expression of miRNA-223 was inversely correlated with expression of IL-35. Finally, the levels of miR-223 and IL-35 were related to Th1/Th2 cytokines, eosinophils count as well as the clinical severity. Our study suggests the potential of miR-223 and IL-35 as a molecular target for the treatment of AR.

Down-regulation of ER-α36 mRNA in serum exosomes of the patients with hepatocellular carcinoma.

Down-regulation of ER-α36 mRNA in serum exosomes of the patients with hepatocellular carcinoma.

MiR-143 promotes angiogenesis and osteoblast differentiation by targeting HDAC7

The regulation of bone formation and detailed mechanisms are still largely elusive, and the roles of microRNAs in this process have attracted much attention. Recently, a specific subtype of CD31hiendomucinhi (CD31hiEMCNhi) endothelium has been identified to promote bone formation, together with osteoblast development. However, the role of microRNA143 in the generation of CD31hi EMCNhi endothelium and bone formation remains unknown. In this study, we found that miR-143 was expressed both in osteoblast cells and CD31hiEMCNhi endothelial cells. Serum miR-143 level was negatively correlated with age in humans. Overexpression of miR-143 promoted osteoblast formation and angiogenic effects. Furthermore, CD31hiEmcnhi vessels and osteoblast formation were significantly inhibited in miR-143 knockout mice. Mechanistically, inhibitor HDAC7 was directly targeted by miR-143 and knockdown of HDAC7 was found to rescue the function of miR-143 deficiency. Thus, miR-143 promotes angiogenesis coupling with osteoblast differentiation by targeting HDAC7, which may serve as a potential target in angiogenic and osteogenic diseases.

Colonic mucosal and serum expression of microRNAs in canine large intestinal inflammatory bowel disease

BackgroundCanine inflammatory bowel disease (IBD) is a group of chronic gastrointestinal (GI) disorders of still largely unknown etiology. Canine IBD diagnosis is time-consuming and costly as other diseases with similar signs should be initially excluded. In human IBD microRNA (miR) expression changes have been reported in GI mucosa and blood. Thus, there is a possibility that miRs may provide insight into disease pathogenesis, diagnosis and even treatment of canine IBD. The aim of this study was to determine the colonic mucosal and serum relative expression of a miRs panel in dogs with large intestinal IBD and healthy control dogs.ResultsCompared to healthy control dogs, dogs with large intestinal IBD showed significantly increased relative expression of miR-16, miR-21, miR-122 and miR-147 in the colonic mucosa and serum, while the relative expression of miR-185, miR-192 and miR-223 was significantly decreased. Relative expression of miR-146a was significantly increased only in the serum of dogs with large intestinal IBD. Furthermore, serum miR-192 and miR-223 relative expression correlated to disease activity and endoscopic score, respectively.ConclusionOur data suggest the existence of dysregulated miRs expression patterns in canine IBD and support the potential future use of serum miRs as useful noninvasive biomarkers.

Clinical value of serum microRNA-195 expression in invasive ductal carcinoma of the breast

BackgroundMicroRNAs (miR) are small molecules, with around 17–25 nucleotides in length. Dysregulation of miRNA expression can be used as a diagnostic biomarker of cancer because of their high stability in human serum. MiR-195 has been implicated as a diagnostic biomarker of breast cancer. Therefore, this study aimed to identify the expression levels of miR-195 and its diagnostic role in patients of breast cancer (BC). MethodsThe expression patterns of miR-195 in the serum was analysed from a total number of 100 female with invasive ductal carcinoma in addition to healthy control subjects. Isolation of total RNA was done, samples were measured using SYBR green-based real-time RT-PCR technology. ResultsCirculating levels of miR-195 were found to be significantly decreased in BC group compared to that of control group (p < 0.001), the serum miR-195 was associated with numerous clinicopathological considerations of breast cancer as serum miR-195 expression decreased significantly in the presence of nodal (p = 0.044) and distant metastasis (p = 0.049) in BC cases, moreover it showed significant negative correlation with tumour stage, grade and primary tumour extent (p < 0.001). Receiver operating characteristic (ROC) curve was conducted for discrimination between BC cases and control groups, miR-195 expression showed excellent AUCs (0.987), with the best cut off value of 0.996, sensitivity was 90%, specificity was 100%, PPV was 100%, NPV was 87% and accuracy was 94%. Regression analysis revealed that higher CA15-3 and lower miRNA195 were considered as independent predictors for BC diagnosis. ConclusionOur data showed that serum miR-195 expressions were down-regulated in breast cancer females; furthermore, this downregulation was associated with higher specificity in diagnosis BC cases and so it could be used as a non-invasive diagnostic marker in BC.

MicroRNA-150 serves as a diagnostic biomarker and is involved in the inflammatory pathogenesis of Parkinson's disease.

BackgroundDysregulation of microRNAs (miRNAs) has been reported to be involved in the neuroinflammatory pathogenesis of PD. This study aimed to investigate the serum expression of microRNA‐150 (miR‐150) in Parkinson's disease (PD) patients and further uncover the regulatory effect of miR‐150 on neuroinflammation.MethodsQuantitative Real‐Time PCR was used to measure the expression of miR‐150. A receiver operating characteristic curve was applied to evaluate the diagnostic value of miR‐150. The effect of miR‐150 on neuroinflammation was analyzed by examining its correlation with proinflammatory cytokines and gain‐of‐function experiments in microglia treated with LPS.ResultsSerum miR‐150 expression was downregulated in PD patients compared with the healthy controls, and served as a candidate diagnostic biomarker for the screening of PD cases. Negative correlation was found between miR‐150 levels and the levels of procytokines in PD patients. By the treatment of LPS, microglia BV2 cells had a reduced expression of miR‐150, and the enhanced neuroinflammatory responses were inhibited by the overexpression of miR‐150. AKT3 was verified as a target of miR‐150 in BV2 cells.ConclusionAll the data of this study revealed that the decreased serum miR‐150 serves as a potential diagnostic biomarker. The methods to increase miR‐150 expression may have a beneficial effect in PD via suppressing the neuroinflammation by targeting AKT3.

MicroRNA-93, upregulated in serum of nasopharyngeal carcinoma patients, promotes tumor cell proliferation by targeting PDCD4.

Deregulation of microRNAs (miRs) has been demonstrated to contribute to the development and malignant progression of nasopharyngeal carcinoma (NPC). Recently, miR-93 was reported to be significantly upregulated in NPC tissues and cell lines, and promote the proliferation, migration and invasion of NPC cells in vitro, as well as tumor growth in vivo. However, whether there is any clinical value of serum miR-93 expression in NPC still remains unclear. Therefore, the present study aimed to explore the clinical significance of serum miR-93 expression in NPC. A total of 85 serum samples from NPC patients and 30 from healthy controls were collected. Reverse transcription-quantitative polymerase chain reaction data demonstrated that the serum expression of miR-93 was significantly increased in NPC patients, when compared with those in healthy controls. Following receiving chemo-radiotherapy, the serum miR-93 levels were significantly decreased in NPC patients. Furthermore, the increased serum levels of miR-93 were significantly associated with advanced grade, clinical stage, lymph node metastasis, as well as worse 5-year overall survival of NPC patients. Furthermore, the serum miR-93 expression was demonstrated to be an independent factor for predicating the prognosis of NPC. In vitro experiments demonstrated that knockdown of miR-93 caused a decrease in NPC cell proliferation, whereas overexpression of miR-93 promoted NPC cell proliferation. PDCD4 was then identified as a direct target of miR-93 in NPC cells. Overexpression of PDCD4 significantly eliminated the promoting effects of miR-93 overexpression on NPC cell proliferation. Taken together, these findings suggest that the serum miR-93 expression could be used as a predicator for the clinical outcome of NPC patients, and suggest that miR-93 may also become a potential therapeutic target for NPC treatment.

Diagnostic significance of serum miR-26b and miR-21 expressions in ovarian cancer and their associations with clinicopathological characteristics and prognosis of patients.

The aim of this study was to detect the expressions of serum micro-ribonucleic acid (miR)-26b and miR-21 in ovarian cancer patients, and to explore their associations with the diagnosis, clinicopathological parameters and prognosis of ovarian cancer. A total of 86 patients diagnosed with ovarian cancer in our hospital from January 2014 to January 2015 were enrolled in the observation group. Meanwhile, another 86 subjects receiving physical examination in our hospital during the same period were enrolled in the control group. The expressions of serum miR-26b and miR-21 in both groups were detected via Real Time fluorescence-quantitative Polymerase Chain Reaction (RT-qPCR). Receiver operating characteristic (ROC) curves were plotted. Later, the clinical diagnostic value of combined detection of miR-26b and miR-21 in ovarian cancer was analyzed. Moreover, the associations of serum miR-26b and miR-21 expressions with clinicopathological characteristics and prognosis of ovarian cancer patients were explored. The expression of serum miR-26b in ovarian cancer patients was significantly lower than that of healthy subjects, while miR-21 expression was markedly higher in ovarian cancer patients (p<0.05). The area under the ROC curve (AUC), the sensitivity and specificity of miR-26b detection, miR-21 detection and combined detection in the diagnosis of ovarian cancer were 0.753 vs. 0.826 vs. 0.916, 47.2 vs. 76.3 vs. 87.6 and 78.5 vs. 85.6 vs. 90.4, respectively. Therefore, it could be observed that both the sensitivity and specificity of combined detection were remarkably higher than those of single detection (p<0.05). In addition, the expressions of serum miR-26b and miR-21 were associated with clinical stage and lymph node metastasis of ovarian cancer patients, whereas it was not correlated with age and histological type. The 3-year survival rate of patients with high expression of serum miR-26b was significantly higher than that in those with low expression of serum miR-26b. However, the 3-year survival rate of patients with low expression of serum miR-21 was higher than that in those with high expression. MiR-21 is highly expressed, while miR-26b is lowly expressed in the serum of ovarian cancer patients. Both of them may be involved in the incidence and development of ovarian cancer. Furthermore, combined monitoring of serum miR-26b and miR-21 has a certain value in the clinical diagnosis and treatment of ovarian cancer.

Circulating miR-203 secreted from metastatic tissues could exacerbate myopenia in colorectal cancer patients.

181 Background: Sarcopenia is commonly observed in advanced cancer patients with distant metastases. In addition, biological functions of microRNAs (miRNAs) in cell-to-cell communication by incorporating into neighboring or distal cells has been gradually elucidated in various diseases, including sarcopenia, have been established. Methods: First, we quantified miR-203 expression, a key miRNA involved in cell-to-cell communication, by qRT-PCR and in situ hybridization in 58 pairs of primary CRC (pCRC) and corresponding matched liver metastasis (LM) tissues. We further evaluated miR-203 levels using pCRC tissues and matched preoperative serum to clarify its clinical significance in independent 183 CRC patients. Second, we assessed psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC) using preoperative computed tomography imaging to clarify its clinical burden and correlations with miR-203 levels in CRC patients. Functional analysis of miR-203 overexpression was investigated in human skeletal muscle cells (SkMC), and cells were analyzed for proliferation and apoptosis. Expression of several, putative, miR-203-target genes was also validated in SkMC cells. Results: MiR-203 expression was significantly upregulated in LM compared with matched pCRC tissues. Serum miR-203 levels were significantly upregulated in a stage-dependent manner, and high miR-203 expression was associated with poor survival in patients with CRC in both patient cohorts. In contrast to IMAC, decreased PMI significantly correlated with well-established disease development factors, and decreased PMI was an independent prognostic factor for both overall survival, and disease-free survival in CRC patients. Although tissue miR-203 expression did not significantly correlate with the body composition status, serum miR-203 expression negatively correlated with preoperative PMI level. Overexpression of miR-203 inhibited cell proliferation and induced apoptosis via downregulation of BIRC5 (Survivin) expression in SkMC cell. Conclusions: Assessment of serum miR-203 could be used for risk assessment of metastasis-related myopenia in CRC.