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.
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.
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.
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.
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.
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.
Lung cancer is the most common cancer worldwide. The outcome and management of lung cancer patients could be improved by early diagnosis and prognosis. MicroRNAs (miRNAs) have been implicated in signaling pathways regulating a variety of biological processes and play important roles in the development of carcinoma. Moreover, miRNAs can exist in the circulation in a remarkably stable form. All of these suggest miRNAs as new potentially clinical biomarkers for diagnosis and prognosis of lung cancer. In this review, we aim to discuss diagnostic and prognostic value and potential clinical utility of miRNAs in serum.
ObjectiveTo investigate the microRNA (miRNA) expression profile during chondrogenic differentiation of human adipose-derived stem cells (hADSCs), and assess the roles of involved miRNAs during chondrogenesis.
MethodshADSCs were harvested and cultured from donors who underwent elective liposuction or other abdominal surgery. When the cells were passaged to P3, chondrogenic induction medium was used for chondrogenic differentiation. The morphology of the cells was observed by inverted phase contrast microscopy. Alcian blue staining was carried out at 21 days after induction to access the chondrogenic status. The expressions of chondrogenic proteins were detected by ELISA at 0, 7, 14, and 21 days. The miRNA expression profiles at pre- and post-chondrogenic induction were obtained by microarray assay, and differentially expressed miRNAs were verified by real-time quantitative PCR (qRT-PCR). The targets of the miRNAs were predicted by online software programs.
ResultshADSCs were cultured successfully and induced with chondrogenic medium. At 21 days after chondrogenic induction, the cells were stained positively for alcian blue staining. At 7, 14, and 21 days after chondrogenic induction, the levels of collogen type Ⅱ, Col2a1, aggrecan, Col10a1, and chondroitin sulfate in induced hADSCs were significantly higher than those in noninduced hADSCs (P<0.05). Eleven differentially expressed miRNAs were found, including seven up-regulated and four down-regulated. Predicted target genes of the differentially expressed miRNAs were based on the overlap from three public prediction algorithms, with the known functions of regulating chondrogenic differentiation of stem cells, selfrenewal, signal transduction, intracellular signaling cascade, and cell cycle control.
ConclusionA group of miRNAs and their target genes are identified, which may play important roles in regulating chondrogenic differentiation of hADSCs. These results will facilitate the initial understanding of the molecular mechanism of chondrogenic differentiation in hADSCs and subsequently control hADSCs differentiation, and provide high performance seed cells for cartilage tissue engineering.
Objective To summarize the domestic and abroad articles related to the research on the relation between microRNA （miRNA） and pancreatic cancer，and explore the important effects of miRNA expression patterns in diagnosis of pancreatic cancer. Methods “microRNA and pancreatic cancer” were searched as key words by PubMed and CNKI series full-text database retrieval systems from 2000 to 2012. Totally 60 English papers and 15 Chinese papers were obtained. Choice criteria：the basic research of miRNA and pancreatic cancer，the clinical research of miRNA and pancreatic cancer， and the prospect of miRNA in pancreatic cancer diagnosis and treatment. According to the choice criteria，31 papers were finally analyzed. Results The miRNA expression spectrum and specific miRNA expression such as miR-21，miR-34，miR-217，miR-196a，miR-10a，miR-155，miR-221，miR-222，miR-181a，miR-181b，miR-181d， and the family members of miR-200 and let-7 might be used as tumor markers to differentiate pancreatic cancer from normal pancreas，chronic pancreatitis or pancreatic endocrine tumors，and might be used as prognostic factor to predict the outcome. Conclusions miRNA expression spectrum are not only related to diagnosis of pancreatic cancer， but also have provided a new research direction and method for gene therapy of pancreatic cancer．
ObjectiveTo investigate the expressions of microRNA-155 (miR-155) in different phenotypes of activated macrophages.
MethodsThe THP-1 cells underwent polarized activation into M1, M2 or tumor-associated macrophages (TAMs), and the phenotypes were confirmed by flow cytometry. The miR-155 expression was determined by qRt-PCR in M1 macrophages, M2 macrophages and TAMs.
ResultsThe miR-155 expression significantly decreased in the M2 macrophages (1.83±0.337, P=0.000), TAMs (1.60±0.233, P=0.000) compared with the M1 (6.580±0.637). The phenotype of TAMs was similar to M2. There was no statistically significant difference between TAMs and M2 macrophages in the expression of miR-155 (P=0.546).
ConclusionDifferent expressions of miR-155 in macrophages M1-type and M2-type may be associated with the differentiation or their cellular functions. The phenotypic characteristics TAMs may transform to macrophages to M2-type. And they may have the same functions.
