Homo sapiens
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PROVIDER: PRJNA123797 | ENA |
REPOSITORIES: ENA
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Project description:MiRNA and lung cancer (INCA project) - 26 RNG25k microarrays
| PRJNA123799 | ENA
Project description:MiRNA and lung cancer (INCA Project) - 16 RNG25k microarrays
| PRJNA123801 | ENA
Project description:Recent studies have identified miR-210 among a set of hypoxia-regulated miRNAs, and shown the central regulatory role played by HIF to control transcription of this miRNA. Contradictory data exist concerning the regulation and roles of miR-210 during cancer progression. miR-210 appears at the same time over-expressed in some solid tumors (breast, pancreas, head and neck carcinomas, gliomas) while often deleted in ovarian carcinoma. It has been shown that depending on the tissue type or cellular model, miR-210 was indeed able to either promote entry into the cell cycle and to inhibit apoptosis or rather repress tumor initiation. We show here deregulation of several miRNAs in human lung cancer biopsies, including an over-expression of miR-210 which appears specific of late-stages of the tumor (>stage 2). MiR-210 function was then analyzed in the lung adenocarcinoma cell line A549. We found that miR-210 induced a delayed inhibition of proliferation associated with an induction of cell death. We also observed that mir-210 induces a loss of mitochondrial membrane potential and the apparition of an aberrant mitochondrial phenotype. mRNA expression profiling of cells overexpressing mir-210 revealed a specific signature characterized by an enrichment in mir-210 predicted targets among the downregulated transcripts (57 out of 243, p<10-12). Functional annotation of this set of mir-210-regulated transcripts, which includes several subunits of Electron Transport Chain (ETC) complex I and complex II revealed enrichment for terms such as 'cell death' and 'mitochondrial dysfunction'. Two of these ETC subunits, predicted to be targets of mir-210 by several bioinformatics prediction tools, were experimentally confirmed after cloning of their respective 3'UTR in a luciferase reporter vector. Finally, we provide experimental evidence indicating that these mitochondrial alterations could modulate HIF via a positive regulatory loop. Overall, our data strongly suggest that mir-210 could mediate two apparently opposite functions: i) apoptosis through targeting of specific mitochondrial components ii) a modulation of HIF through a positive regulatory loop. We propose that this dual behavior can explain the contradictory data regarding the impact of miR-210 during cancer progression. Refer to individual Series. This SuperSeries is composed of the following subset Series: GSE18692: MiRNA and lung cancer (INCA project) - 40 miRNAs microarrays GSE18694: MiRNA and lung cancer (INCA project) - 26 RNG25k microarrays GSE18695: MiRNA and lung cancer (INCA Project) - 66 RNG25k microarrays
2010-09-30 | E-GEOD-18805 | biostudies-arrayexpress
Project description:We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. We report that the majority of miRNA genes encode mature isomers that vary in size by one or more bases at the 3’ and/or 5’ end of the miRNA. Northern blotting for individual miRNAs showed that the proportions of isomiRs expressed by a single miRNA gene often differ between cell and tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo and were active in luciferase assays, indicating that they are functional. Bioinformatics analysis predicts substantial differences in targeting between miRNAs with minor 5’ differences and in support of this we report that a 5’ isomiR-9-1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use of isomiR-specific sponges. Our analysis of the miRGator database indicates that a small percentage of human miRNA genes express isomiRs as the dominant transcript in certain cell types and analysis of miRBase shows that 5’ isomiRs have replaced canonical miRNAs many times during evolution. This strongly indicates that isomiRs are of functional importance and have contributed to the evolution of miRNA genes
2014-08-06 | GSE58734 | GEO
Project description:41 lung adenocarcinoma from never-smokers hybridized on Illumina SNP arrays on 13 HumanCNV370-Quadv3 chips. High-resolution array comparative genomic hybridization analysis of lung adenocarcinoma in 41 never smokers for identification of new minimal common regions (MCR) of gain or loss. The SNP array analysis validated copy-number aberrations and revealed that RB1 and WRN were altered by recurrent copy-neutral loss of heterozygosity.The present study has uncovered new aberrations containing cancer genes. The oncogene FUS is a candidate gene in the 16p region that is frequently gained in never smokers. Multiple genetic pathways defined by gains of MYC, deletions of RB1 and WRN or gains on 7p and 7q are involved in lung adenocarcinoma in never smokers. A 'Cartes d'Identite des Tumeurs' (CIT) project from the French National League Against Cancer (http://cit.ligue-cancer.net) 41 samples hybridized on Illumina SNP arrays. Submitter : Fabien PETEL petelf@ligue-cancer.net . Project leader : Pr Pierre FOURET pierre.fouret@psl.aphp.fr
2011-07-28 | E-TABM-1169 | biostudies-arrayexpress
Project description:We have sequenced miRNA libraries from human embryonic, neural and foetal mesenchymal stem cells. We report that the majority of miRNA genes encode mature isomers that vary in size by one or more bases at the 3’ and/or 5’ end of the miRNA. Northern blotting for individual miRNAs showed that the proportions of isomiRs expressed by a single miRNA gene often differ between cell and tissue types. IsomiRs were readily co-immunoprecipitated with Argonaute proteins in vivo and were active in luciferase assays, indicating that they are functional. Bioinformatics analysis predicts substantial differences in targeting between miRNAs with minor 5’ differences and in support of this we report that a 5’ isomiR-9-1 gained the ability to inhibit the expression of DNMT3B and NCAM2 but lost the ability to inhibit CDH1 in vitro. This result was confirmed by the use of isomiR-specific sponges. Our analysis of the miRGator database indicates that a small percentage of human miRNA genes express isomiRs as the dominant transcript in certain cell types and analysis of miRBase shows that 5’ isomiRs have replaced canonical miRNAs many times during evolution. This strongly indicates that isomiRs are of functional importance and have contributed to the evolution of miRNA genes Sequence library of miRNAs from a single sample of human foetal mesenchymal stem cells. Results tested and confirmed by northern blotting. Please note that only raw data files are available for the embryonic and neual samples and thus, directly submitted to SRA (SRX547311, SRX548700, respectively under SRP042115/PRJNA247767)
2014-08-06 | E-GEOD-58734 | biostudies-arrayexpress
Project description:By combining extensive biochemical fractionation with quantitative mass spectrometry, we directly examined the composition of soluble multiprotein complexes among diverse animal models. The project has been jointly supervised by Andrew Emili and Edward M. Marcotte. Project website: http://metazoa.med.utoronto.ca
2015-07-22 | PXD002322 | Pride
Project description:This project analyzes peripheral miRNA blood profiles of patients with lung diseases. Since miRNAs are known to be valuable diagnostic markers we asked whether respective patterns of lung cancer patients and COPD patients can be detected in peripheral blood samples rather than in biopsies. The project aimed at an impoved understanding of complex profiles rather than single markers. Thus, a high-throughput technique was necessary, profiling all known miRNAs integratively. n = 19 normal controls, n = 28 lung cancer patients and n = 24 COPD samples have been screened for the complete miRNA repertoire. Please note that each miRNA has been measured in seven replicates and the median of the replica has been computed.
2011-03-11 | E-GEOD-24709 | biostudies-arrayexpress
Project description:This project analyzes peripheral miRNA blood profiles of patients with lung diseases. Since miRNAs are known to be valuable diagnostic markers we asked whether respective patterns of lung cancer patients and COPD patients can be detected in peripheral blood samples rather than in biopsies. The project aimed at an impoved understanding of complex profiles rather than single markers. Thus, a high-throughput technique was necessary, profiling all known miRNAs integratively.
2011-03-11 | GSE24709 | GEO
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature