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  • 1
    Abstract: Long noncoding RNAs (lncRNAs) are emerging as regulators of gene expression in pathogenesis, including cancer. Recently, lncRNAs have been implicated in progression of specific subtypes of breast cancer. One aggressive, basal-like subtype associates with increased EGFR signaling, while another, the HER2-enriched subtype, engages a kin of EGFR Based on the premise that EGFR-regulated lncRNAs might control the aggressiveness of basal-like tumors, we identified multiple EGFR-inducible lncRNAs in basal-like normal cells and overlaid them with the transcriptomes of over 3,000 breast cancer patients. This led to the identification of 11 prognostic lncRNAs. Functional analyses of this group uncovered LINC01089 (here renamed LncRNA Inhibiting Metastasis; LIMT), a highly conserved lncRNA, which is depleted in basal-like and in HER2-positive tumors, and the low expression of which predicts poor patient prognosis. Interestingly, EGF rapidly downregulates LIMT expression by enhancing histone deacetylation at the respective promoter. We also find that LIMT inhibits extracellular matrix invasion of mammary cells in vitro and tumor metastasis in vivo In conclusion, lncRNAs dynamically regulated by growth factors might act as novel drivers of cancer progression and serve as prognostic biomarkers.
    Type of Publication: Journal article published
    PubMed ID: 27485121
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  • 2
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The most common human cancers are malignant neoplasms of the skin. Incidence of cutaneous melanoma is rising especially steeply, with minimal progress in non-surgical treatment of advanced disease. Despite significant effort to identify independent predictors of melanoma outcome, no ...
    Type of Medium: Electronic Resource
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  • 3
    Publication Date: 2016-01-28
    Description: To investigate gene specificity at the level of translation in both the human genome and viruses, we devised a high-throughput bicistronic assay to quantify cap-independent translation. We uncovered thousands of novel cap-independent translation sequences, and we provide insights on the landscape of translational regulation in both humans and viruses. We find extensive translational elements in the 3' untranslated region of human transcripts and the polyprotein region of uncapped RNA viruses. Through the characterization of regulatory elements underlying cap-independent translation activity, we identify potential mechanisms of secondary structure, short sequence motif, and base pairing with the 18S ribosomal RNA (rRNA). Furthermore, we systematically map the 18S rRNA regions for which reverse complementarity enhances translation. Thus, we make available insights into the mechanisms of translational control in humans and viruses.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Weingarten-Gabbay, Shira -- Elias-Kirma, Shani -- Nir, Ronit -- Gritsenko, Alexey A -- Stern-Ginossar, Noam -- Yakhini, Zohar -- Weinberger, Adina -- Segal, Eran -- New York, N.Y. -- Science. 2016 Jan 15;351(6270). pii: aad4939. doi: 10.1126/science.aad4939. Epub 2016 Jan 14.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel. Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel. ; The Delft Bioinformatics Laboratory, Department of Intelligent Systems, Delft University of Technology, Delft, Netherlands. Platform Green Synthetic Biology, Delft, Netherlands. Kluyver Centre for Genomics of Industrial Fermentation, Delft, Netherlands. ; Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel. ; Department of Computer Science, Technion, Haifa, Israel. Agilent Laboratories, Tel-Aviv, Israel. ; Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel. Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel. eran.segal@weizmann.ac.il.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26816383" target="_blank"〉PubMed〈/a〉
    Keywords: 3' Untranslated Regions/genetics ; 5' Untranslated Regions/genetics ; Base Pairing ; Gene Expression Regulation, Viral ; Genome, Human/*genetics ; Genome, Viral/*genetics ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Internal Ribosome Entry Sites/genetics ; Mutagenesis ; Oligonucleotides/chemistry/genetics ; Protein Biosynthesis/*genetics ; RNA Caps/*genetics ; RNA Viruses/genetics ; RNA, Ribosomal, 18S/genetics/metabolism ; Sequence Analysis, DNA/methods ; Sequence Analysis, RNA/methods
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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