1,082 research outputs found
Exploring genetic associations with ceRNA regulation in the human genome
No full textabstract: Competing endogenous RNAs (ceRNAs) are RNA molecules that sequester shared microRNAs (miRNAs) thereby affecting the expression of other targets of the miRNAs. Whether genetic variants in ceRNA can affect its biological function and disease development is still an open question. Here we identified a large number of genetic variants that are associated with ceRNA's function using Geuvaids RNA-seq data for 462 individuals from the 1000 Genomes Project. We call these loci competing endogenous RNA expression quantitative trait loci or ‘cerQTL’, and found that a large number of them were unexplored in conventional eQTL mapping. We identified many cerQTLs that have undergone recent positive selection in different human populations, and showed that single nucleotide polymorphisms in gene 3΄UTRs at the miRNA seed binding regions can simultaneously regulate gene expression changes in both cis and trans by the ceRNA mechanism. We also discovered that cerQTLs are significantly enriched in traits/diseases associated variants reported from genome-wide association studies in the miRNA binding sites, suggesting that disease susceptibilities could be attributed to ceRNA regulation. Further in vitro functional experiments demonstrated that a cerQTL rs11540855 can regulate ceRNA function. These results provide a comprehensive catalog of functional non-coding regulatory variants that may be responsible for ceRNA crosstalk at the post-transcriptional level.The final version of this article, as published in Nucleic Acids Research, can be viewed online at: https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkx33
The construction and analysis of ceRNA networks in invasive breast cancer: a study based on The Cancer Genome Atlas
No full textChundi Gao,1,* Huayao Li,1,* Jing Zhuang,2,3 HongXiu Zhang,4 Kejia Wang,5 Jing Yang,2 Cun Liu,6 Lijuan Liu,2,3 Chao Zhou,2,3 Changgang Sun2,3 1College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250014, People’s Republic of China; 2Department of Oncology, Weifang Traditional Chinese Hospital, Weifang 261041, People’s Republic of China; 3Department of Oncology, Affiliated Hospital of Weifang Medical University, Weifang 261031, People’s Republic of China; 4Institute of Virology, Jinan Center for Disease Control and Prevention, Jinan 250021, People’s Republic of China; 5College of Basic Medicine, Qingdao University, Qingdao 266071, People’s Republic of China; 6College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250014, People’s Republic of China *These authors contributed equally to this work Background: Studies have shown that long noncoding RNAs (lncRNAs) make up the major proportion of the ceRNA network and can regulate gene expression by competitively binding to miRNAs. This reveals the existence of an RNA-miRNA regulatory pathway and is of great biological significance. CeRNAs, as competitive endogenous RNAs, have revealed a new mechanism of interaction between RNAs. Until now, the role of lncRNA-mediated ceRNAs in breast cancer and their regulatory mechanisms have been elucidated to some extent. Purpose: In this study, comprehensive analysis of large-scale invasive breast cancer samples in TCGA were conducted to further explore the developmental mechanism of invasive breast cancer and the potential predictive markers for invasive breast cancer prognosis in the ceRNA network. Methods: Abnormal expression profiles of invasive breast cancer associated mRNAs, lncRNAs and miRNAs were obtained from the TCGA database. Through further alignment and prediction of target genes, an abnormal lncRNA-miRNA-mRNA ceRNA network was constructed for invasive breast cancer. Through the overall survival analysis, Identification prognostic biomarkers for invasive breast cancer patients，In addition, we used Cytoscape plug-in BinGo for the different mRNA performance functional cluster analysis. Results: Differential analysis revealed that 1059 lncRNAs, 86 miRNAs, and 2138 mRNAs were significantly different in invasive breast cancer samples versus normal samples. Then we construct an abnormal lncRNA-miRNA-mRNA ceRNA network for invasive breast cancer, consisting of 90 DElncRNAs, 18 DEmiRNAs and 26 DEmRNAs.Further, 4 out of 90 lncRNAs, 3 out of 26 mRNAs, and 2 out of 18 miRNAs were useful as prognostic biomarkers for invasive breast cancer patients (P value < 0.05). It is worth noting that based on the ceRNA network, we found that the LINC00466-Hsa-mir-204- NTRK2 LINC00466-hsa-mir-204-NTRK2 axis was present in 9 RNAs associated with the prognosis of invasive breast cancer. Conclusion: This study provides an effective bioinformatics basis for further understanding of the molecular mechanism of invasive breast cancerand for predicting outcomes, which can guide the use of invasive breast cancerdrugs and subsequent related research. Keywords: invasive breast cancer, cancer genome atlas, lncRNA–miRNA–mRNA ceRNA network, bioinformatics, diagnosis and prognosis biomarker
Integrated analysis of lncRNA-miRNA-mRNA ceRNA network in human aortic dissection
No full textAbstract Background Many studies on long chain non-coding RNAs (lncRNAs) are published in recent years. But the roles of lncRNAs in aortic dissection (AD) are still unclear and should be further examined. The present work focused on determining the molecular mechanisms underlying lncRNAs regulation in aortic dissection on the basis of the lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network. Methods This study collected the lncRNAs (GSE52093), mRNAs (GSE52093) and miRNAs (GSE92427) expression data within human tissue samples with aortic dissection group and normal group based on Gene Expression Omnibus (GEO) database. Results This study identified three differentially expressed lncRNAs (DELs), 19 differentially expressed miRNAs (DEmiRs) and 1046 differentially expressed mRNAs (DEGs) identified regarding aortic dissection. Furthermore, we constructed a lncRNA-miRNA-mRNA network through three lncRNAs (including two with up-regulation and one with down-regulation), five miRNAs (five with up-regulation), as well as 211 mRNAs (including 103 with up-regulation and 108 with down-regulation). Simultaneously, we conducted functional enrichment and pathway analyses on genes within the as-constructed ceRNA network. According to our PPI/ceRNA network and functional enrichment analysis results, four critical genes were found (E2F2, IGF1R, BDNF and PPP2R1B). In addition, E2F2 level was possibly modulated via lncRNA FAM87A-hsa-miR-31-5p/hsa-miR-7-5p or lncRNA C9orf106-hsa-miR-7-5p. The expression of IGF1R may be regulated by lncRNA FAM87A-hsa-miR-16-5p/hsa-miR-7-5p or lncRNA C9orf106-hsa-miR-7-5p. Conclusion In conclusion, the ceRNA interaction axis we identified is a potentially critical target for treating AD. Our results shed more lights on the possible pathogenic mechanism in AD using a lncRNA-associated ceRNA network
Role of the long non-coding RNA PVT1 in the dysregulation of the ceRNA-ceRNA network in human breast cancer
No full textRecent findings have identified competing endogenous RNAs (ceRNAs) as the drivers in many disease conditions, including cancers. The ceRNAs indirectly regulate each other by reducing the amount of microRNAs (miRNAs) available to target messenger RNAs (mRNAs). The ceRNA interactions mediated by miRNAs are modulated by a titration mechanism, i.e. large changes in the ceRNA expression levels either overcome, or relieve, the miRNA repression on competing RNAs; similarly, a very large miRNA overexpression may abolish competition. The ceRNAs are also called miRNA decoys or miRNA sponges and encompass different RNAs competing with each other to attract miRNAs for interactions: mRNA, long non-coding RNAs (lncRNAs), pseudogenes, or circular RNAs. Recently, we developed a computational method for identifying ceRNA-ceRNA interactions in breast invasive carcinoma. We were interested in unveiling which lncRNAs could exert the ceRNA activity. We found a drastic rewiring in the cross-talks between ceRNAs from the physiological to the pathological condition. The main actor of this dysregulated lncRNA-associated ceRNA network was the lncRNA PVT1, which revealed a net biding preference towards the miR-200 family members in normal breast tissues. Despite its up-regulation in breast cancer tissues, mimicked by the miR-200 family members, PVT1 stops working as ceRNA in the cancerous state. The specific conditions required for a ceRNA landscape to occur are still far from being determined. Here, we emphasized the importance of the relative concentration of the ceRNAs, and their related miRNAs. In particular, we focused on the withdrawal in breast cancer tissues of the PVT1 ceRNA activity and performed a gene expression and sequence analysis of its multiple isoforms. We found that the PVT1 isoform harbouring the binding site for a representative miRNA of the miR-200 family shows a drastic decrease in its relative concentration with respect to the miRNA abundance in breast cancer tissues, providing a plausibility argument to the breakdown of the sponge program orchestrated by the oncogene PVT1. © 2017 Conte et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
Exploring functional variation affecting miRNA and ceRNA regulation in humans
No full textMicroRNA (miRNA) sponges have been shown to function as competing endogenous RNAs (ceRNAs) to regulate the expression of other miRNA targets in the network by sequestering available miRNAs. As the first systematic investigation of the genome-wide genetic effect on ceRNA regulation, we applied multivariate response regression and identified widespread genetic variations that are associated with ceRNA competition using 462 Geuvadis RNA-seq data in multiple human populations. We showed that SNPs in gene 3’UTRs at the miRNA seed binding regions can simultaneously regulate gene expression changes in both cis and trans by the ceRNA mechanism. We termed these loci as endogenous miRNA sponge expression quantitative trait loci or “emsQTLs”, and found that a large number of them were unexplored in conventional eQTL mapping. We identified many emsQTLs are undergoing recent positive selection in different human populations. Using GWAS results, we found that emsQTLs are significantly enriched in traits/diseases associated loci. Functional prediction and prioritization extend our understanding on causality of emsQTL allele in disease pathways. We illustrated that emsQTL can synchronously regulate the expression of tumor suppressor and oncogene through ceRNA competition in angiogenesis. Together these results provide a distinct catalog and characterization of functional noncoding regulatory variants that control ceRNA crosstalk.link_to_OA_fulltex
DRMs, Innovation and Creation
No full textDRMs are intellectual property institutions. They transpose the empirical principle of copyright, which implicitly recognizes that specific ownership rules should be attached to non scientific creation, into the digital era. The legal protection of DRMs, a private means of enforcing content excludability, participates in the "privatization" of copyright protection. This, in turn, means that a proprietary software — governed by intellectual property rights, reinforced by public law — becomes the key to the vertical relations shaped by exclusive copyright. DRMs consequently represent a major stake in the competition to capture network effects in the content distribution vertical chaincopyright; distribution; DRMs; network effects
A network-based matrix factorization framework for ceRNA co-modules recognition of cancer genomic data
No full text\ua9 The Author(s) 2022. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected]. With the development of high-throughput technologies, the accumulation of large amounts of multidimensional genomic data provides an excellent opportunity to study the multilevel biological regulatory relationships in cancer. Based on the hypothesis of competitive endogenous ribonucleic acid (RNA) (ceRNA) network, lncRNAs can eliminate the inhibition of microRNAs (miRNAs) on their target genes by binding to intracellular miRNA sites so as to improve the expression level of these target genes. However, previous studies on cancer expression mechanism are mostly based on individual or two-dimensional data, and lack of integration and analysis of various RNA-seq data, making it difficult to verify the complex biological relationships involved. To explore RNA expression patterns and potential molecular mechanisms of cancer, a network-regularized sparse orthogonal-regularized joint non-negative matrix factorization (NSOJNMF) algorithm is proposed, which combines the interaction relations among RNA-seq data in the way of network regularization and effectively prevents multicollinearity through sparse constraints and orthogonal regularization constraints to generate good modular sparse solutions. NSOJNMF algorithm is performed on the datasets of liver cancer and colon cancer, then ceRNA co-modules of them are recognized. The enrichment analysis of these modules shows that >90% of them are closely related to the occurrence and development of cancer. In addition, the ceRNA networks constructed by the ceRNA co-modules not only accurately mine the known correlations of the three RNA molecules but also further discover their potential biological associations, which may contribute to the exploration of the competitive relationships among multiple RNAs and the molecular mechanisms affecting tumor development
Christina M. Cerna on The Torture Papers: The Road to Abu Ghraib. Edited by Karen J. Greenberg and Joshua L. Dratel. Cambridge, MA: Cambridge University Press, 2005. 1249 pp.
No full textA review of:
The Torture Papers: The Road to Abu Ghraib. Edited by Karen J. Greenberg and Joshua L. Dratel. Cambridge, MA: Cambridge University Press, 2005. 1249 pp
Conditions of Development of a Product Ecolabel
No full textSince the early 1990s, national ecolabelling programmes have proliferated worldwide. The European Union (EU) implemented such a regional program in 1991. This decision was part of a broader orientation towards Integrated Product Policy approach in the EU. Since 1991, the development of European ecolabels has been slow and difficult. This paper examines industrial strategies vis-à-vis the EU ecolabel in order to understand the problems faced by the regulator in the development of this ecolabel.The first part of the paper defines and uses the concept of credence good in order to argue that the consumer cannot assess the ecolabel. Based on the examination of the development of the European ecolabel, the second part points out three variables that seem to influence the development of product eco-labels : i) the type of industry (i.e. the degree of heterogeneity between the sets of products sold by the different firms); ii) the threat of direct governmental regulation on the environmental quality of the product; and, iii) the magnitude of the final demand for a green variant of the product. The paper concludes with a discussion of on policy implications for policy makers interested in considering or promoting the use of ecolabels.quality, eco-labeling, voluntary environmental regulation.
The Crisis And Central Bank Reaction
No full textThe world economy is in the face of the strongest crisis of the last seventy years. This crisis is still ongoing, but authorities in many countries have already taken a series of measures to mitigate the effects. In this fight, the central banks are the first line. It is still too early to draw any lessons from the events taking place, but a reflection "sine ira et studio" over this experience is already possible. This paper aims to analyze this experience through the policies implemented by central banks to cope with the crisis.central bank, crisis, liquidity, regulation
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