ObjectiveTo investigate the impact and mechanism of over-expression microRNA-92a (miR-92a) in clinicopathologic feature and prognosis of patients with colorectal cancer (CRC). MethodsThe expression levels of miR-92a and phosphatase and tensin homologue (PTEN) gene in 108 cases of colorectal cancer tissues were detected by using real-time fluorescent quantitative PCR (RT-PCR), and they were categorized as low or high in relation to the median value. Then the association between different levels of miR-92a gene expression and clinicopathologic feature and prognosis of CRC patients were evaluated. Moreover, the relationship between the expressions of miR-92a and PTEN gene were analyzed. ResultsHigh expression of miR-92a not only associated with lymph node metastasis (χ2=8.045, P=0.007), distant metastasis (χ2=5.708, P=0.030), and TNM staging (χ2=6.366, P=0.019) of CRC patients, but also related to the down-regulated of PTEN gene expression (χ2=21.333, P < 0.001). However, up-regulated miR-92a expression was negatively correlated with age, gender, tumor size, tumor location, depth of invasion and tumor differentiation. In addition, Kaplan-Meier survival curves showed that over-expression of miR-92a and low-expression of PTEN gene could potentially predict poor overall survival of CRC patients. ConclusionThe high expression of miR-92a can lead to a poor clinical prognosis of CRC patients through decreasing the expression level of PTEN gene.
Considering the low accuracy of prediction in the positive samples and poor overall classification effects caused by unbalanced sample data of MicroRNA (miRNA) target, we proposes a support vector machine (SVM)-integration of under-sampling and weight (IUSM) algorithm in this paper, an under-sampling based on the ensemble learning algorithm. The algorithm adopts SVM as learning algorithm and AdaBoost as integration framework, and embeds clustering-based under-sampling into the iterative process, aiming at reducing the degree of unbalanced distribution of positive and negative samples. Meanwhile, in the process of adaptive weight adjustment of the samples, the SVM-IUSM algorithm eliminates the abnormal ones in negative samples with robust sample weights smoothing mechanism so as to avoid over-learning. Finally, the prediction of miRNA target integrated classifier is achieved with the combination of multiple weak classifiers through the voting mechanism. The experiment revealed that the SVM-IUSW, compared with other algorithms on unbalanced dataset collection, could not only improve the accuracy of positive targets and the overall effect of classification, but also enhance the generalization ability of miRNA target classifier.
Objective To review the regulation of microRNA-17-92 cluster on bone development, remodeling, and metabolism. Methods The related literature was reviewed. The clinical genetic phenotype, animal experiment, and cell research were illustrated so as to explore the possible regulatory mechanisms. Results MicroRNA-17-92 cluster is involved in physiological normal organs development, pathological neoplasm occurrence, and development. Recently, studies have shown that microRNA-17-92 cluster constitutes an intricate molecular signaling network with its upstream transcription factors and downstream targeting proteins, which controls bone development, remodeling, and metabolism exquisitely. Conclusion Present fundamental researches have certain understanding of the regulatory mechanisms of microRNA-17-92 cluster on bone development, remodeling, and metabolism. However, the exact mechanisms under these processes remain unknown.
ObjectiveTo investigate the changes of lung function after exposure to fine particulate matter (PM2.5) for 60 days and the expression of miR-146 in mice.MethodsThirty SPF BALB/c mice were treated with noninvasive tracheal instillation of fine particulate matter suspension at different doses (2.5 mg/kg, 5.0 mg/kg, 10.0 mg/kg) for 2 months (two times one week), the blank group and normal saline group were set as control groups. The mice were examined and killed on the next day after the last instillation. Histopathological changes of the lungs, pro-infammatory factors levels in the lung tissues, pulmonary functions and the relative expression of miR-146a and miR-146b in the lung tissues were detected.ResultsPeak inspiratory flow (PIF) and peak expiratory flow (PEF) were decreased significantly after PM2.5 exposure, however, lung resistance increased and maximal voluntary ventilation reduced from the general tendency without significant difference. Hematoxylin-eosin stain showed lymphocyte infiltration and macrophage infiltration by phagocytic particles, alveolar spacer widening, inflammatory response increased with the increase of PM2.5 exposure dosage. Pro-infammatory factors as interleukin-6 in the bronchoalveolar lavage fluid, interferon-γ and tumor necrosis factor-α in the lung homogenate were increased significantly by enzyme linked immunosorbent assay. The relative expressions of miR-146a and miR-146b were up-regulated remarkablely in treatment groups compared to the control group by real-time fluorescence quantitative polymerase chain reaction, which had negative relationships with PIF and PEF.ConclusionsThe lung function of mice decreases significantly after exposure to fine particulate matter, and the expression of miR-146 is up-regulated.
ObjectiveTo systematically evaluate the clinical value of miRNA-1 in the diagnosis of acute myocardial infarction (AMI) patients.MethodsWe searched PubMed, EMbase, Cochrane Library, CNKI, Wangfang, VIP, etc databases to identify literature about miRNA-1 in the diagnosis of AMI. Quality of the included literature was assessed by (quality assessment for diagnostic accuracy studies-2, QUADAS-2). The indices of pooled sensitivity (Sen), specificity (Spe), positivity likelihood ratio (PLR), negative likelihood ratio (NLR), diagnosis odds ratio (DOR), and the area under the summary receiver operating characteristic (SROC) curve were pooled using MetaDisc 1.4 software.ResultsA total of 12 articles were included. According to the different populations of miRNA-1 to be tested, subgroup analysis of healthy people (7 articles) and non-AMI disease groups (5 articles) was conducted. The results showed that AMI compared with healthy people, the pooled Sen was 0.78 with 95%CI 0.73 to 0.82, Spe was 0.88 with 95%CI 0.83 to 0.91 of miRNA-1 in the diagnosis of AMI. AUC of SROC curve was 0.911 2. Comparison of AMI and non-AMI patients, the pooled Sen was 0.59 with 95%CI 0.54 to 0.64, Spe was 0.74 with 95%CI 0.68 to 0.79 of miRNA-1 in the diagnosis of AMI. AUC of SROC curve was 0.743 2.ConclusionMiRNA-1 has a certain value in the diagnosis of AMI. It has an advantage in identifying AMI and patients with other systemic diseases, and can be combined with other biomarkers to diagnose AMI.
Vascular endothelial cell(VEC) is a kind of simple squamous epithelium lined on the inner surface of blood vessels. VEC is an important barrier between the blood and tissue and it also plays a key role in regulating inflammation, thrombosis, endothelial cells mediated vasodilatation and endothelial regeneration. These processes should be controlled by a variety of complex mechanism which requires us to find out. With results of the researches in vascular endothelial cell function, the important roles that microRNA in vascular endothelial cell function draws more and more researchers' attention. MicroRNAs control gene expression in post-transcriptional level and affect the function of endothelial cells. This review focuses on the research progress on regulatory mechanism of microRNA to endothelial cell inflammation, thrombosis, vasodilation and endothelium regeneration.
Abstract： Objective To observe the expression changes of microRNA 1 （miRNA-1） and microRNA 21（miRNA-21） after ischemic preconditioning （IPC）, ischemic postconditioning （IPO） and remote ischemic preconditioning （RIPC）in an ischemia-reperfusion rat heart model in vitro, as well as the expression of their target protein heat shock protein 70 （HSP70） and programmed cell death 4 （PDCD4）, and evaluate whether miRNA are involved in endogenous cardio-protective mechanism. Methods The Langendorff-perfused Sprague-Dawley rat hearts were randomly assigned into one of the four groups, control group （CON group, n=12）, ischemia preconditioning group （IPC group， n=12）?, ischemia postconditioning group （IPO group， n=12） and remote ischemia preconditioning group （RIPC group，n=12）. Cardiac function was digitalized and analyzed. The expression of HSP70, PDCD4, B-cell lymphoma/leukemia-2 （Bcl-2） and Bax was detected by Western blotting. The expression of miRNA-1 and miRNA-21 was detected by real-time reverse transcriotion-polymerase chain reaction （RT-PCR）. Assessment of cardiac infarct size and myocardial apoptosis was determined using triphenyltetrazolium chloride （TTC） assay and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay （TUNEL） assay respectively. Results The expressions of miRNA-1 and miRNA-21 were up-regulated in IPC group, but the expression of miRNA-1 was down-regulated in RIPC group and IPO group （P＜0.05）. The expressionsof PDCD4, HSP70 and Bax were down-regulated in ‘conditioning’ groups compared with CON group （P＜0.05）. The expression of Bcl-2 was not statistically different among the four groups. The infarct size and the myocardial apoptosis in ‘conditioning’ hearts were significantly decreased compared with CON group （P＜0.05）. Conclusion The expressions of the miRNA-1 and miRNA-21 are different in IPC, RIPC and IPO groups, and their target proteins are not inversely correlated with the miRNAs in all the ‘conditioning’ groups.
Objective To summarize the relationship of diabetes and its complications with microRNA. Methods Domestic and international researches were collected by searching to summarize the role of microRNA in diabetes and its complications. Results MicroRNA could affect the secretion of insulin and interfer metabolism of gulcose in fat cells， muscle cells， and liver cells， which resulting in insulin resistance. At the same time， the microRNA also played an role in damage of vascular endothelial cells and myocardial cell in diabetes. Conclusion MicroRNA acts an important role in the process of diabetes and its complications.
Objective To explore the induction of cardiomyogenesis of microRNA-129 （mir-129） in rat bone marrowmesenchymal stem cells （BM-MSCs） and its mechanism. Methods BM-MSCs were isolated from Sprague-Dawley rats and cultured in vitro. Overexpression of mir-129 or both mir-129 and glycogen synthase kinase-3β （GSK-3β） in BM-MSCs was produced with a lentiviral vector system. All the BM-MSCs were divided into four groups: control group （MSCs），Lentiviral vectors＋MSCs group （Lv-MSCs），mir-129 transfection group （mir-129-MSCs），and mir-129＋GSK-3βdouble transfection group （mir-129＋GSK-3β-MSCs）. Five-Azacytidine （5-Aza） （10 μmol/L） was used to induce BM-MSCsdifferentiation into cardiomyocytes. On the 1st，5 th，10 th，15 th and 20 th day after induction，realtime-PCR was performedto detect mRNA levels of GATA-4，Nkx2.5 and MEF-2C. On the 10 th，15 th and 20 th day after induction，Western blottingwas performed to examine expression levels of cTnI，Desmin，GSK-3β，phosphorylated β-catenin and dephosphorylated β-catenin. Results Compared with the control group，at respective time points，mRNA levels of cardiomyogenic genes and expression levels of cardiomyocyte-related proteins of mir-129 transfection group were significantly elevated，theexpression level of GSK-3β was significantly decreased，and the ratio of dephosphorylated/phosphorylated β-catenin was significantly elevated. When both mir-129 and GSK-3β were overexpressed in BM-MSCs，mRNA levels of cardiomyogenicgenes and expression levels of cardiomyocyte-related proteins were significantly lower than those of mir-129 transfection group，and the ratio of dephosphorylated/phosphorylated β-catenin was significantly decreased. Conclusion Overexpression of mir-129 can promote cardiomyogenesis of rat BM-MSCs possibly via inhibiting GSK-3β production and thus decreasing the inhibition of phosphorylation of β-catenin which then enters the nucleus and activates downstream signaling pathways that regulate cardiomyogenic differentiation of BM-MSCs.
Age-related macular degeneration (AMD) is a multifactorial disease affected by environmental factors and genetic variation, which is a major cause of irreversible vision loss in the elderly. miRNA is a kind of endogenous non-coding RNA, which plays an important role in the pathogenesis of AMD, such as oxidative stress, pathological neovascularization and inflammation, by inhibiting or silencing the expression of transcription genes. miRNA has unique advantages in terms of ease synthesis, targeting and additive effect, a large number of experiments have proved the therapeutic potential of miRNA in AMD, which is expected to become a new method for the treatment of AMD in the future. Since the pathogenesis of AMD has not been fully elucidated, it is still necessary to continue to study the pathogenesis of AMD, the biological effects and mechanisms of various miRNA in the occurrence and development of AMD, and observe its therapeutic effects in AMD, so as to provide more effective options for the precise prevention and treatment of AMD.