共查询到20条相似文献,搜索用时 15 毫秒
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An integrative genomic approach identifies p73 and p63 as activators of miR-200 microRNA family transcription 总被引:1,自引:0,他引:1
Knouf EC Garg K Arroyo JD Correa Y Sarkar D Parkin RK Wurz K O'Briant KC Godwin AK Urban ND Ruzzo WL Gentleman R Drescher CW Swisher EM Tewari M 《Nucleic acids research》2012,40(2):499-510
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RNA polymerase III transcribes human microRNAs 总被引:1,自引:0,他引:1
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Zheng Y Xiong S Jiang P Liu R Liu X Qian J Zheng X Chu Y 《Free radical biology & medicine》2012,52(8):1307-1317
Glucocorticoids (GCs) are among the most widely used and effective therapies for many chronic inflammatory diseases. Although attempts have been made to identify important protein-coding genes and pathways involved in the anti-inflammatory effect of GCs, knowledge of genomic aberrations associated with noncoding genes, such as micro-RNAs (miRNAs), and their contributions is relatively limited. In this study, a systematic screening of the miRNA expression profile by microarray showed that GCs inhibited the expression of miR-155 in lipopolysaccharide (LPS)-induced macrophage inflammatory responses. Overexpression of miR-155 markedly reversed the suppressive action of GCs, whereas inhibition of miR-155 exhibited an effect similar to that of GCs on LPS-treated RAW264.7 cells, indicating miR-155 to be a functional regulator in the anti-inflammatory effect of GCs. Furthermore, GCs inhibited miR-155 expression in a GC receptor- and NF-κB-dependent manner. Bioinformatics analysis and luciferase assay revealed that the NF-κB binding site located in the promoter region of the B-cell integration cluster was important in mediating the GC-driven suppression of miR-155 in response to LPS stimulation. In addition, the combination of treatment with GCs and inhibition of miR-155 enhanced the anti-inflammatory effect of GCs on LPS-stimulated RAW264.7 cells. Therefore, we identify miR-155 to be a novel target through which GCs exert their anti-inflammatory effect on the LPS-induced macrophage inflammatory response. These findings may provide a basic rationale for new approaches in the effort to develop anti-inflammatory therapeutics. 相似文献
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Chunlong Zhang Chunquan Li Jing Li Junwei Han Desi Shang Yunpeng Zhang Wei Zhang Qianlan Yao Lei Han Yanjun Xu Wei Yan Zhaoshi Bao Gan You Tao Jiang Chunsheng Kang Xia Li 《PloS one》2014,9(5)
The prognosis of glioma patients is usually poor, especially in patients with glioblastoma (World Health Organization (WHO) grade IV). The regulatory functions of microRNA (miRNA) on genes have important implications in glioma cell survival. However, there are not many studies that have investigated glioma survival by integrating miRNAs and genes while also considering pathway structure. In this study, we performed sample-matched miRNA and mRNA expression profilings to systematically analyze glioma patient survival. During this analytical process, we developed pathway-based random walk to identify a glioma core miRNA-gene module, simultaneously considering pathway structure information and multi-level involvement of miRNAs and genes. The core miRNA-gene module we identified was comprised of four apparent sub-modules; all four sub-modules displayed a significant correlation with patient survival in the testing set (P-values≤0.001). Notably, one sub-module that consisted of 6 miRNAs and 26 genes also correlated with survival time in the high-grade subgroup (WHO grade III and IV), P-value = 0.0062. Furthermore, the 26-gene expression signature from this sub-module had robust predictive power in four independent, publicly available glioma datasets. Our findings suggested that the expression signatures, which were identified by integration of miRNA and gene level, were closely associated with overall survival among the glioma patients with various grades. 相似文献
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Regulatory elements responsible for inducible expression of the granulocyte colony-stimulating factor gene in macrophages. 下载免费PDF全文
Granulocyte colony-stimulating factor (G-CSF) plays an essential role in granulopoiesis during bacterial infection. Macrophages produce G-CSF in response to bacterial endotoxins such as lipopolysaccharide (LPS). To elucidate the mechanism of the induction of G-CSF gene in macrophages or macrophage-monocytes, we have examined regulatory cis elements in the promoter of mouse G-CSF gene. Analyses of linker-scanning and internal deletion mutants of the G-CSF promoter by the chloramphenicol acetyltransferase assay have indicated that at least three regulatory elements are indispensable for the LPS-induced expression of the G-CSF gene in macrophages. When one of the three elements was reiterated and placed upstream of the TATA box of the G-CSF promoter, it mediated inducibility as a tissue-specific and orientation-independent enhancer. Although this element contains a conserved NF-kappa B-like binding site, the gel retardation assay and DNA footprint analysis with nuclear extracts from macrophage cell lines demonstrated that nuclear proteins bind to the DNA sequence downstream of the NF-kappa B-like element, but not to the conserved element itself. The DNA sequence of the binding site was found to have some similarities to the LPS-responsive element which was recently identified in the promoter of the mouse class II major histocompatibility gene. 相似文献
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Background
Natural or endogenous sense/antisense miRNAs, located on sense and antisense strands in the same genomic region, respectively, are detected recently. However, little is known about these miRNA pairs, especially for their distributions in different animal species. We herein present systematic analysis of them in human, mouse and rat miRNAs, and their expression patterns based on deep sequencing datasets.Methods and results
The phenomenon of miRNA–miRNA interaction could be detected in different animal species. The common miRNAs pairs were found across species. These miRNA pairs could form miRNA:miRNA duplex with complete complementary structure, and were prone to be located on specific chromosomes. They might be homologous miRNA genes (especially in human), or clustered in a gene cluster (especially in rat), or simultaneously detected in different genomic regions due to multicopy pre-miRNAs. Remarkably, some miRNA pairs, located in different genomic regions, also showed complementarity as well as endogenous sense/antisense miRNAs. Based on published deep sequencing datasets, one member of miRNA pairs always was abundantly expressed, whereas another was quite rare. Rare common target mRNAs of these miRNA pairs were predicted.Conclusions
Interaction between miRNAs and significant expression divergence implied complex potential mutual regulatory pattern in the miRNA world. The study would enrich miRNA regulatory network. 相似文献13.
The transcriptional regulator network of human inflammatory macrophages is defined by open chromatin
Susanne V Schmidt Wolfgang Krebs Thomas Ulas Jia Xue Kevin Ba?ler Patrick Günther Anna-Lena Hardt Hartmut Schultze Jil Sander Kathrin Klee Heidi Theis Michael Kraut Marc Beyer Joachim L Schultze 《Cell research》2016,26(2):151-170
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Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells 总被引:1,自引:0,他引:1
Marson A Levine SS Cole MF Frampton GM Brambrink T Johnstone S Guenther MG Johnston WK Wernig M Newman J Calabrese JM Dennis LM Volkert TL Gupta S Love J Hannett N Sharp PA Bartel DP Jaenisch R Young RA 《Cell》2008,134(3):521-533
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Skalsky RL Samols MA Plaisance KB Boss IW Riva A Lopez MC Baker HV Renne R 《Journal of virology》2007,81(23):12836-12845
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Macrophage polarization contributes to the initiation and perpetuation of systemic lupus erythematosus (SLE). Our previous study demonstrated that M2b polarized macrophages induced by activated lymphocyte-derived DNA (ALD-DNA) have a crucial function in the initiation and progress of SLE disease. Accumulated data suggest that microRNAs (miRNAs) serve as critical regulators to control macrophage polarization. To investigate miRNA regulation during macrophage M2b polarization of SLE, miRNA microarrays of murine bone marrow derived macrophages (BMDMs) were performed following stimulation with ALD-DNA for 6 and 36 h. Over 11% of the 1111 analyzed miRNAs appeared differentially expressed during ALD-DNA triggered macrophage M2b polarization. Cluster analysis revealed certain patterns in miRNA expression that are closely linked to ALD-DNA induced macrophage M2b polarization. Analysis of the network structure showed that the predicted functions of the differentially regulated miRNAs at 6 h are significantly associated with inflammatory response and disease. Differentially regulated miRNAs identified at 36 h were determined to be significantly related to cell proliferation by biological network analysis. In this study, dynamic miRNA expression patterns and network analysis are described for the first time during ALD-DNA induced macrophage M2b polarization. The data not only provide a better understanding of miRNA-mediated macrophage polarization but also demonstrate the future therapeutic potential of targeting miRNAs in SLE patients. 相似文献