miRNA 206 and miRNA 574-5p are highly expression in coronary artery disease

Coronary artery disease (CAD) is the leading cause of human morbidity and mortality worldwide. Innovative diagnostic biomarkers are a pressing need for this disease. miRNAs profiling is an innovative method of identifying biomarkers for many diseases and could be proven as a powerful tool in the diagnosis and treatment of CAD. We performed miRNA microarray analysis from the plasma of three CAD patients and three healthy controls. Subsequently, we performed quantitative real-time PCR (qRT-PCR) analysis of miRNA expression in plasma of another 67 CAD patients and 67 healthy controls. We identified two miRNAs (miR-206 and miR-574-5p) that were significantly up-regulated in CAD patients as compared with healthy controls (P<0.05). The receiver operating characteristic (ROC) curves indicated these two miRNAs had great potential to provide sensitive and specific diagnostic value for CAD.     

Circulating microRNAs,miR‐92a,miR‐100 and miR‐143, as non‐invasive biomarkers for bladder cancer diagnosis

The application of microRNAs (miRNAs) as potential biomarkers and therapy targets has been widely investigated in many kinds of cancers. Recent advantages of serum miRNAs open a new realm of possibilities for non‐invasive diagnosis and prognosis of bladder cancer (BC). The aim of our study was to identify plasma miR‐92a, miR‐100 and miR‐143 expression signatures in patients with BC to introduce new markers for establishing BC diagnosis and prognosis. Blood samples were collected from 70 BC patients and 62 controls. An expression of three target miRNAs (miR‐92a, miR‐100 and miR‐143) was measured using quantitative real‐time PCR method. Results were correlated with clinicopathological data and analysed. Plasma levels of miR‐92a, miR‐100 and miR‐143 were significantly lower in BC patients than in control group. Receiver operator characteristic analysis revealed that the sensitivity and specificity values of miR‐92a were 97·1% and 76·7%, respectively, with a cut‐off value of 0·573. The sensitivity and specificity values of miR‐100 were 90% and 66·7%, respectively, with a cut‐off value of 0·644. The sensitivity and specificity values of miR‐143 were 78·6% and 93·3%, respectively, with a cut‐off value of 0·164. This study explores the existence of specific plasma miRNAs as early diagnostic biomarkers for BC in Egyptian patients; and these findings suggest that plasma miR‐92a, miR‐100 and miR‐143 could be promising novel circulating biomarkers in clinical detection of BC. Copyright © 2016 John Wiley & Sons, Ltd.     

Dysregulated circRNAs in plasma from active tuberculosis patients

Endogenous circular RNAs (circRNAs) have been reported in various diseases. However, their role in active TB remains unknown. The study was aimed to determine plasma circRNA expression profile to characterize potential biomarker and improve our understanding of active TB pathogenesis. CircRNA expression profiles were screened by circRNA microarrays in active TB plasma samples. Dysregulated circRNAs were then verified by qRT‐PCR. CircRNA targets were predicted based on analysis of circRNA‐miRNA‐mRNA interaction. GO and KEGG pathway analyses were used to predict the function of circRNA. ROC curve was calculated to evaluate diagnostic value for active TB. A total of 75 circRNAs were significantly dysregulated in active TB plasma. By further validation, hsa_circRNA_103571 exhibited significant decrease in active TB patients and showed potential interaction with active TB‐related miRNAs such as miR‐29a and miR‐16. Bioinformatics analysis revealed that hsa_circRNA_103571 was primarily involved in ras signalling pathway, regulation of actin cytoskeleton, T‐ and B‐cell receptor signalling pathway. ROC curve analysis suggested that hsa_circRNA_103571 had significant value for active TB diagnosis. Circulating circRNA dysregulation may play a role in active TB pathogenesis. Hsa_circRNA_103571 may be served as a potential biomarker for active TB diagnosis, and hsa_circRNA_103571‐miRNA‐mRNA interaction may provide some novel mechanism for active TB.     

Circulating microRNAs as diagnostic and therapeutic biomarkers in gastric and esophageal cancers

Gastric and esophageal cancers are as main cancers of the gastrointestinal (GI) tract, which are associated with poor diagnosis and survival. Several efforts were made in the past few decades to finding effective therapeutic approaches, but these approaches had several problems. Finding new biomarkers is a critical step in finding new approaches for the treatment of these cancers. Finding new biomarkers that cover various aspects of the diseases could provide a choice of suitable therapies and better monitoring of patients with these cancers. Among several biomarkers tissue specific and circulating microRNAs (miRNAs) have emerged as powerful candidates in the diagnosis of gastric and esophageal cancers. MiRNAs are small noncoding single‐stranded RNA molecules that are found in the blood and regulate gene expression. These have numerous characteristics that make them suitable for being used as ideal biomarkers in cancer diagnosis. Research has indicated that the level and profile of miRNA in serum and plasma are very high. They are potentially noninvasive and sensitive enough to detect tumors in their primary stages of infection. Multiple lines of evidence indicate that the presence, absence, or deregulation of several circulating miRNAs (i.e., let‐7a, miR‐21, miR‐93, miR‐192a, miR‐18a, and miR‐10b for gastric cancer, and miR‐21, miR‐375, miR‐25‐3p, miR‐151a‐3p, and miR‐100‐3p for esophageal cancer) are associated with initiation and progression of gastric and esophageal cancers. The aim of this review is to highlight the recent advances in the roles of miRNAs in diagnosis and treatment of gastric and esophageal cancers.     

Atherosclerosis-Related Circulating miRNAs as Novel and Sensitive Predictors for Acute Myocardial Infarction

Background

The dysregulated expressions of circulating miRNAs have been detected in various cardiovascular diseases. In our previous experiments, the altered expressions of circulating miRNA-21-5p, miRNA-361-5p and miRNA-519e-5p were confirmed in patients with coronary atherosclerosis by miRNA microarrays. However, the expression levels of these circulating miRNAs in the early phase of acute myocardial infarction (AMI) are still unknown. In the present study, our aims were to examine the expressions of circulating miR-21-5p, miR-361-5p and miR-519e-5p in AMI patients, and assess their clinical applications for diagnosing and monitoring AMI.

Results

Two different cohorts were enrolled in this study. The first cohort included 17 AMI patients and 28 healthy volunteers, and the second cohort included 9 AMI patients, 9 ischemic stroke patients, 8 patients with pulmonary embolism, and 12 healthy volunteers. Quantitative real-time PCR and ELISA assays were preformed to detect the concentrations of plasma miRNAs and cardiac troponin I (cTnI), respectively. The results showed that the plasma levels of miR-21-5p and miR-361-5p were significantly increased in AMI patients, whereas the concentration of circulating miR-519e-5p was reduced. Interestingly, the levels of these circulating miRNAs correlated with the concentrations of plasma cTnI. Receiver operating characteristic (ROC) analysis revealed that these three circulating miRNAs had considerable diagnostic accuracy for AMI with high values of area under ROC curve (AUC). Importantly, combining the three miRNAs significantly increased the diagnostic accuracy. Furthermore, cell experiments demonstrated that these plasma miRNAs may originate from injured cardiomyocytes induced by hypoxia. In addition, the levels of all the three circulating miRNAs in ischemic stroke (IS) and pulmonary embolism (PE) were elevated, whereas the decreased level of plasma miR-519e-5p was only detected in AMI. ROC analysis demonstrated that circulating miR-519e-5p may be a useful biomarker for distinguishing AMI from other ischemic diseases.

Conclusions

Circulating miRNAs may be novel and powerful biomarkers for AMI and they could be potential diagnostic tool for AMI.     

Cellular and extracellular miRNAs are blood‐compartment‐specific diagnostic targets in sepsis

Septic shock is a common medical condition with a mortality approaching 50% where early diagnosis and treatment are of particular importance for patient survival. Novel biomarkers that serve as prompt indicators of sepsis are urgently needed. High‐throughput technologies assessing circulating microRNAs represent an important tool for biomarker identification, but the blood‐compartment specificity of these miRNAs has not yet been investigated. We characterized miRNA profiles from serum exosomes, total serum and blood cells (leukocytes, erythrocytes, platelets) of sepsis patients by next‐generation sequencing and RT‐qPCR (n = 3 × 22) and established differences in miRNA expression between blood compartments. In silico analysis was used to identify compartment‐specific signalling functions of differentially regulated miRNAs in sepsis‐relevant pathways. In septic shock, a total of 77 and 103 miRNAs were down‐ and up‐regulated, respectively. A majority of these regulated miRNAs (14 in serum, 32 in exosomes and 73 in blood cells) had not been previously associated with sepsis. We found a distinctly compartment‐specific regulation of miRNAs between sepsis patients and healthy volunteers. Blood cellular miR‐199b‐5p was identified as a potential early indicator for sepsis and septic shock. miR‐125b‐5p and miR‐26b‐5p were uniquely regulated in exosomes and serum, respectively, while one miRNA (miR‐27b‐3p) was present in all three compartments. The expression of sepsis‐associated miRNAs is compartment‐specific. Exosome‐derived miRNAs contribute significant information regarding sepsis diagnosis and survival prediction and could serve as newly identified targets for the development of novel sepsis biomarkers.     

The potential of microRNAs as human prostate cancer biomarkers: A meta‐analysis of related studies

Prostate cancer (PC) is a very important kind of male malignancies. When PC evolves into a stage of hormone resistance or metastasis, the fatality rate is very high. Currently, discoveries and advances in miRNAs as biomarkers have opened the potential for the diagnosis of PC, especially early diagnosis. miRNAs not only can noninvasively or minimally invasively identify PC, but also can provide the data for optimization and personalization of therapy. Moreover, miRNAs have been shown to play an important role to predict prognosis of PC. The purpose of this meta‐analysis is to integrate the currently published expression profile data of miRNAs in PC, and evaluate the value of miRNAs as biomarkers for PC. All of relevant records were selected via electronic databases: Pubmed, Embase, Cochrane, and CNKI based on the assessment of title, abstract, and full text. we extracted mean ± SD or fold change of miRNAs expression levels in PC versus BPH or normal controls. Pooled hazard ratios (HRs) with 95% confidence intervals (CI) for overall survival (OS) and recurrence‐free survival (RFS), were also calculated to detect the relationship between high miRNAs expression and PC prognosis. Selected 104 articles were published in 2007‐2017. According to the inclusion criteria, 104 records were included for this meta‐analysis. The pooled or stratified analyze showed 10 up‐regulated miRNAs (miR‐18a, miR‐34a, miR‐106b, miR‐141, miR‐182, miR‐183, miR‐200a/b, miR‐301a, and miR‐375) and 14 down‐regulated miRNAs (miR‐1, miR‐23b/27b, miR‐30c, miR‐99b, miR‐139‐5p, miR‐152, miR‐187, miR‐204, miR‐205, miR‐224, miR‐452, miR‐505, and let‐7c) had relatively good diagnostic and predictive potential to discriminate PC from BPH/normal controls. Furthermore, high expression of miR‐32 and low expression of let‐7c could be used to differentiate metastatic PC from local/primary PC. Additional interesting findings were that the expression profiles of five miRNAs (miR‐21, miR‐30c, miR‐129, miR‐145, and let‐7c) could predict poor RFS of PC, while the evaluation of miR‐375 was associated with worse OS. miRNAs are important regulators in PC progression. Our results indicate that miRNAs are suitable for predicting the different stages of PC. The detection of miRNAs is an effective way to control patient's prognosis and evaluate therapeutic efficacy. However, large‐scale detections based on common clinical guidelines are still necessary to further validate our conclusions, due to the bias induced by molecular heterogeneity and differences in study design and detection methods.     

MicroRNA expression profile in serum reveals novel diagnostic biomarkers for endometrial cancer

Purpose: Circulating microRNAs (miRNAs) prove to be promising diagnostic biomarkers for various cancers, including endometrial cancer (EC). The present study aims to identify serum microRNAs that can serve as potential biomarkers for EC diagnosis.Patients and methods: A total of 92 EC and 102 normal control (NC) serum samples were analyzed using quantitative real-time polymerase chain reaction (qRT-PCR) in this four-phase experiment. The logistic regression method was used to construct a diagnostic model based on the differentially expressed miRNAs in serum. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic value. To further validate the diagnostic capacity of the identified signature, the 6-miRNA marker was compared with previously reported biomarkers and verified in three public datasets. In addition, the expression characteristics of the identified miRNAs were further explored in tissue and serum exosomes samples.Results: Six miRNAs (miR-143-3p, miR-195-5p, miR-20b-5p, miR-204-5p, miR-423-3p, and miR-484) were significantly overexpressed in the serum of EC compared with NCs. Areas under the ROC of the 6-miRNA signatures were 0.748, 0.833, and 0.967 for the training, testing, and the external validation phases, respectively. The identified signature has a very stable diagnostic performance in the large cohorts of three public datasets. Compared with previously identified miRNA biomarkers, the 6-miRNA signature in the present study has superior performance in diagnosing EC. Moreover, the expression of miR-143-3p and miR-195-5p in tissues and the expression of miR-20b-5p in serum exosomes were consistent with those in serum.Conclusions: We established a 6-miRNA signature in serum and they could function as potential non-invasive biomarker for EC diagnosis.     

Differential expression of microRNA in serum fractions and association of Argonaute 1 microRNAs with heart failure

The serum or plasma microRNA (miRNA) molecules have been suggested as diagnostic and prognostic biomarkers, in various pathological conditions. However, these molecules are also found in different serum fractions, such as exosomes and Argonaute (Ago) protein complexes. Ago1 is the predominant Ago protein expressed in heart tissue. The objective of the study was to examine the hypothesis that Ago1‐associated miRNAs may be more relevant to cardiac disease and heart failure compared with the serum. In total, 84 miRNA molecules were screened for their expression in the whole serum, exosomes and Ago1, and Ago2 complexes. Ago1‐bound miR‐222‐3p, miR‐497‐5p and miR‐21‐5p were significantly higher, and let‐7a‐5p was significantly lower in HF patients compared with healthy controls, whereas no such difference was observed for those markers in the serum samples among the groups. A combination of these 4 miRNAs into an Ago1‐HF score provided a ROC curve with an AUC of 1, demonstrating clear discrimination between heart failure patients and healthy individuals. Ago1 fraction might be a better and more specific platform for identifying HF‐related miRNAs compared with the whole serum.     

From Moderately Severe to Severe Hypertriglyceridemia Induced Acute Pancreatitis: Circulating MiRNAs Play Role as Potential Biomarkers

The incidence of hypertriglyceridemia induced acute pancreatitis (HTAP) continues to rise in China. It has systemic complications and high mortality, making the early assessment of the severity of this disease even more important. Circulating microRNAs (miRNAs) could be novel, non-invasive biomarkers for disease progression judgment. This study aimed to identify the potential role of serum miRNAs as novel biomarkers of HTAP progression. HTAP patients were divided into two groups: moderately severe (HTMSAP) and severe (HTSAP), healthy people were used as control group. The serum miRNA expression profiles of these three groups were determined by microarray and verified by qRT-PCR. The functions and pathways of the targeted genes of deregulated miRNAs were predicted, using bioinformatics analysis; miRNA-mRNA network was generated. Moreover, the correlation between miR-181a-5p and pancreatitis metabolism related substances were studied and the serum concentration of inflammatory cytokines and miRNAs at different time points during the MSAP and SAP were investigated, respectively. Finally, the receiver operating characteristic (ROC) curve of miRNAs was studied. Significant changes in the serum concentration of the following miRNAs of HTAP patients (P<0.05) were discovered: miR24-3p, 361-5p, 1246, and 222-3p (constantly upregulated), and 181a-5p (constantly downregulated) (P<0.05). Bioinformatics analysis predicted that 13 GOs and 36 pathways regulated by overlap miRNAs were involved in glucose, fat, calcium (Ca++), and insulin metabolism (P<0.001). miRNA-mRNA network revealed that the overlap miRNAs targeted genes participating in pancreas metabolism and miR-181a-5p, the only downregulated miRNA, had good negative correlation with triglyceride (TG), total cholesterol (TC), and fast blood glucose (FBG), but a positive correlation with Ca++. When compared with inflammatory cytokines, the changes of all five overlap miRNAs were more stable. It was found that when used for evaluating the progression of HTAP, miRNAs showed good AUC. These data suggested that serum miRNAs have the potential to be excellent HTAP biomarkers.     

MicroRNA and mRNA expression profiling in metastatic melanoma reveal associations with BRAF mutation and patient prognosis

The role of microRNAs (miRNAs) in melanoma is unclear. We examined global miRNA expression profiles in fresh‐frozen metastatic melanomas in relation to clinical outcome and BRAF mutation, with validation in independent cohorts of tumours and sera. We integrated miRNA and mRNA information from the same samples and elucidated networks associated with outcome and mutation. Associations with prognosis were replicated for miR‐150‐5p, miR‐142‐3p and miR‐142‐5p. Co‐analysis of miRNA and mRNA uncovered a network associated with poor prognosis (PP) that paradoxically favoured expression of miRNAs opposing tumorigenesis. These miRNAs are likely part of an autoregulatory response to oncogenic drivers, rather than drivers themselves. Robust association of miR‐150‐5p and the miR‐142 duplex with good prognosis and earlier stage metastatic melanoma supports their potential as biomarkers. miRNAs overexpressed in association with PP in an autoregulatory fashion will not be suitable therapeutic targets.     

Differential expression of microRNAs in TM3 Leydig cells of mice treated with brain‐derived neurotrophic factor

Brain‐derived neurotrophic factor (BDNF) is a neurotrophin that can promote the development and proliferation of neurons. BDNF has been found to be involved in male reproduction. Leydig cells in testicular interstitial tissues can secrete testosterone in a luteinizing hormone‐dependent manner. We showed that BDNF and its receptor TrkB were expressed in mice TM3 Leydig cells in the present study. Furthermore, BDNF can promote proliferation of mouse TM3 Leydig cells in vitro. Results of microRNA (miRNA) deep sequencing showed that BDNF can alter the expression profile of miRNAs in TM3 Leydig cells. Eighty‐three miRNAs were significantly different in the BDNF‐treated and control groups (fold change of >2.0 or <0.5, P < 0.05) wherein 40 were upregulated and 43 were downregulated. The expression levels of miR‐125a‐5p, miR‐22‐5p, miR‐342‐59, miR‐451a, miR‐148a‐5p, miR‐29b‐3p, miR‐199b‐5p, and miR‐145a‐5p were further confirmed by quantitative real‐time polymerase chain reaction. Bioinformatic analysis revealed that miRNAs regulated a large number of genes with different functions. Pathway analysis indicated that miRNAs participate in the pathways involved in signal transduction, cancer, metabolism, endocrine system, immune system, and nerve system. This study indicated that miRNAs might be involved in the BDNF‐regulated cellular functions of Leydig cells.     

Circulating microRNA signatures serve as potential diagnostic biomarkers for Helicobacter pylori infection

Helicobacter pylor (H pylori), a Gram-negative, microaerobic human pathogen, has been found to be involved in many gastroduodenal diseases. Accurate diagnosis of H pylori infection is a vital part of the effective management of gastroduodenal diseases. Circulating microRNAs (miRNAs) have shown the potential to be used as noninvasive biomarkers for the diagnosis of infectious diseases. The aim of this study was to explore plasma miRNAs as noninvasive biomarkers for H pylori infection. We performed a plasma miRNA expression profile using Illumina high-throughput sequencing and validated the levels of differentially expressed miRNAs in the plasma of 63 H pylori-infected patients and 41 healthy volunteers by quantitative real-time polymerase chain reaction (qRT-PCR). The sequencing results showed that 37 miRNAs were upregulated in the H pylori-infected patients compared with that in the healthy volunteers, while six miRNAs were downregulated. qRT-PCR and receiver operator characteristic analysis suggested that the expression of miR-28-3p, miR-143-3p, miR-151a-3p, and miR-148a-3p were closely associated with H pylori infection. Therefore, the four plasma miRNA panels mentioned above could serve as promising noninvasive biomarkers of H pylori infection.     

Serum miRNAs are potential biomarkers for the detection of disc degeneration,among which miR‐26a‐5p suppresses Smad1 to regulate disc homeostasis

Disc degeneration is a common clinical condition in which damaged discs cause chronic pain; however, a laboratory diagnosis method for its detection is not available. As circulating miRNAs have potential as biomarkers, their application in disc degeneration has not been explored. Here, we prepared serum miRNAs from a mouse disc degeneration model and performed miRNA‐Seq and quantitative PCR to characterize disc degeneration–associated miRNAs. We identified three miRNAs, including miR‐26a‐5p, miR‐122‐5p and miR‐215‐5p, undergoing perturbation during the pathogenesis of disc degeneration. Specifically, the levels of miR‐26a‐5p in the serum demonstrated steady increases in the model of disc degeneration, compared with those in the pre‐injury samples of younger age or compared with normal controls of the same age but without disc degeneration, whereas the miRNAs miR‐122‐5p and miR‐215‐5p exhibited lower expression in post‐injury samples than in their counterparts without the surgery. Moreover, we found that miR‐26a‐5p targets Smad1 expression, and Smad1 negatively regulates Vegfa expression in disc cells, and thus, miR‐26a‐5p promotes disc degeneration. In summary, we established a method that consistently profiles circulating miRNAs and identified multiple miRNAs as promising biomarkers for disc degeneration, among which miR‐26a‐5p enhances VEGF expression during disc degeneration through targeting Smad1 signalling.     

Differential expression of basal microRNAs’ patterns in human dental pulp stem cells

MicroRNAs (miRNAs) are small non‐coding RNAs that regulate translation of mRNA into protein and play a crucial role for almost all biological activities. However, the identification of miRNAs from mesenchymal stem cells (MSCs), especially from dental pulp, is poorly understood. In this study, dental pulp stem cells (DPSCs) were characterized in terms of their proliferation and differentiation capacity. Furthermore, 104 known mature miRNAs were profiled by using real‐time PCR. Notably, we observed 19 up‐regulated miRNAs and 29 significantly down‐regulated miRNAs in DPSCs in comparison with bone marrow MSCs (BM‐MSCs). The 19 up‐regulated miRNAs were subjected to ingenuity analysis, which were composed into 25 functional networks. We have chosen top 2 functional networks, which comprised 10 miRNA (hsa‐miR‐516a‐3p, hsa‐miR‐125b‐1‐3p, hsa‐miR‐221‐5p, hsa‐miR‐7, hsa‐miR‐584‐5p, hsa‐miR‐190a, hsa‐miR‐106a‐5p, hsa‐mir‐376a‐5p, hsa‐mir‐377‐5p and hsa‐let‐7f‐2‐3p). Prediction of target mRNAs and associated biological pathways regulated by each of this miRNA was carried out. We paid special attention to hsa‐miR‐516a‐3p and hsa‐miR‐7‐5p as these miRNAs were highly expressed upon validation with qRT‐PCR analysis. We further proceeded with loss‐of‐function analysis with these miRNAs and we observed that hsa‐miR‐516a‐3p knockdown induced a significant increase in the expression of WNT5A. Likewise, the knockdown of hsa‐miR‐7‐5p increased the expression of EGFR. Nevertheless, further validation revealed the role of WNT5A as an indirect target of hsa‐miR‐516a‐3p. These results provide new insights into the dynamic role of miRNA expression in DPSCs. In conclusion, using miRNA signatures in human as a prediction tool will enable us to elucidate the biological processes occurring in DPSCs.     

MiR‐139‐5p,miR‐940 and miR‐193a‐5p inhibit the growth of hepatocellular carcinoma by targeting SPOCK1

The study was aimed to screen out miRNAs with differential expression in hepatocellular carcinoma (HCC), and to explore the influence of the expressions of these miRNAs and their target gene on HCC cell proliferation, invasion and apoptosis. MiRNAs with differential expression in HCC were screened out by microarray analysis. The common target gene of these miRNAs (miR‐139‐5p, miR‐940 and miR‐193a‐5p) was screened out by analysing the target genes profile (acquired from Targetscan) of the three miRNAs. Expression levels of miRNAs and SPOCK1 were determined by quantitative real time polymerase chain reaction (qRT‐PCR). The target relationships were verified by dual luciferase reporter gene assay and RNA pull‐down assay. Through 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide,thiazolyl blue tetrazolium bromide (MTT) and transwell assays and flow cytometry, HCC cell viability, invasion and apoptosis were determined. In vivo experiment was conducted in nude mice to investigate the influence of three miRNAs on tumour growth. Down‐regulation of miR‐139‐5p, miR‐940 and miR‐193a‐5p was found in HCC. Overexpression of these miRNAs suppressed HCC cell viability and invasion, promoted apoptosis and inhibited tumour growth. SPOCK1, the common target gene of miR‐139‐5p, miR‐940 and miR‐193a‐5p, was overexpressed in HCC. SPOCK1 overexpression promoted proliferation and invasion, and restrained apoptosis of HCC cells. MiR‐139‐5p, miR‐940 and miR‐193a‐5p inhibited HCC development through targeting SPOCK1.     

Platelets in patients with premature coronary artery disease exhibit upregulation of miRNA340* and miRNA624*

Background

Coronary artery disease (CAD) is the leading cause of human morbidity and mortality worldwide, underscoring the need to improve diagnostic strategies. Platelets play a major role, not only in the process of acute thrombosis during plaque rupture, but also in the formation of atherosclerosis itself. MicroRNAs are endogenous small non-coding RNAs that control gene expression and are expressed in a tissue and disease-specific manner. Therefore they have been proposed to be useful biomarkers. It remains unknown whether differences in miRNA expression levels in platelets can be found between patients with premature CAD and healthy controls.

Methodology/Principal Findings

In this case-control study we measured relative expression levels of platelet miRNAs using microarrays from 12 patients with premature CAD and 12 age- and sex-matched healthy controls. Six platelet microRNAs were significantly upregulated (miR340*, miR451, miR454*, miR545:9.1. miR615-5p and miR624*) and one miRNA (miR1280) was significantly downregulated in patients with CAD as compared to healthy controls. To validate these results, we measured the expression levels of these candidate miRNAs by qRT-PCR in platelets of individuals from two independent cohorts; validation cohort I consisted of 40 patients with premature CAD and 40 healthy controls and validation cohort II consisted of 27 patients with artery disease and 40 healthy relatives. MiR340* and miR624* were confirmed to be upregulated in patients with CAD as compared to healthy controls in both validation cohorts.

Conclusion/Significance

Two miRNAs in platelets are significantly upregulated in patients with CAD as compared to healthy controls. Whether the two identified miRNAs can be used as biomarkers and whether they are cause or consequence of the disease remains to be elucidated in a larger prospective study.