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dc.contributor.authorRamos, Kenneth S.
dc.contributor.authorMoore, Sara
dc.contributor.authorRunge, Isabel
dc.contributor.authorTavera-Garcia, Marco A.
dc.contributor.authorCascone, Ilaria
dc.contributor.authorCourty, Jose
dc.contributor.authorReyes-Reyes, Elsa M.
dc.date.accessioned2020-01-31T22:27:38Z
dc.date.available2020-01-31T22:27:38Z
dc.date.issued2020-01-01
dc.identifier.citationRamos KS, Moore S, Runge I, Tavera-Garcia MA, Cascone I, Courty J, Reyes-Reyes EM. The Nucleolin Antagonist N6L Inhibits LINE1 Retrotransposon Activity in Non-Small Cell Lung Carcinoma Cells. J Cancer 2020; 11(3):733-740. doi:10.7150/jca.37776. Available from http://www.jcancer.org/v11p0733.htmen_US
dc.identifier.issn1837-9664
dc.identifier.doi10.7150/jca.37776
dc.identifier.urihttp://hdl.handle.net/10150/636826
dc.description.abstractLung cancer is the most common cause of cancer death in the United States. The genome of non-small cell lung cancer (NSCLC), the most frequent lung cancer type, is strongly affected by Long Interspersed Nuclear Element (LINE1) insertions. Active LINE1s are repetitive DNA sequences that can amplify themselves in the genome utilizing a retrotransposition mechanism whereby LINE1 is copied via reverse transcription and inserted at target sites. ORF1p and ORF2p are LINE1 encoded proteins essential for LINE1 retrotransposition. LINE1s are silenced epigenetically in somatic tissues, and their reactivation has been associated with cancer pathogenesis. Here, we present evidence that nucleolin (NCL) regulates expression of LINE1-ORF1p (L1-ORF1p) in NSCLC cells. Genetic knockdown of NCL significantly inhibited expression of L1-ORF1p in various NSCLC cell lines. Treatment with the investigational NCL antagonist N6L ablated L1-ORF1p expression in all cell lines constitutively expressing L1-ORFp. N6L displayed a stronger antiproliferative activity in NSCLC tumor cell lines expressing the highest L1-ORF1p protein levels. Moreover, N6L treatment of nude mice bearing NSCLC tumor xenografts blocked L1-ORF1p expression and effectively inhibited tumor growth. These data indicate that L1-ORF1p expression is regulated by NCL and identify NCL as a novel promising target for pharmacological inhibition of LINE1.en_US
dc.description.sponsorshipAmerica Cancer Society [IRG-16-124-37]; University of Arizona Career Development Award; GURI Award; Agence National pour la RechercheFrench National Research Agency (ANR) [ANR-16 CE17-0023]en_US
dc.language.isoenen_US
dc.publisherIVYSPRING INT PUBLen_US
dc.rightsCopyright © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectNucleolinen_US
dc.subjectLINE1en_US
dc.subjectNSCLCen_US
dc.subjectLung canceren_US
dc.titleThe Nucleolin Antagonist N6L Inhibits LINE1 Retrotransposon Activity in Non-Small Cell Lung Carcinoma Cellsen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Coll Med, Dept Med, Div Pulm Allergy Crit Care & Sleep Meden_US
dc.contributor.departmentUniv Arizona, Ctr Canc, Dept Cellular & Mol Meden_US
dc.identifier.journalJOURNAL OF CANCERen_US
dc.description.noteOpen access journalen_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
dc.source.volume11
dc.source.issue3
dc.source.beginpage733-740
refterms.dateFOA2020-01-31T22:27:38Z


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Copyright © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).
Except where otherwise noted, this item's license is described as Copyright © The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).