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dc.creatorGuijo, Macarenaes
dc.creatorCeballos Chávez, Maríaes
dc.creatorGómez Marín, Elenaes
dc.creatorBasurto Cayuela, Lauraes
dc.creatorReyes, José C.es
dc.date.accessioned2019-01-15T13:18:05Z
dc.date.available2019-01-15T13:18:05Z
dc.date.issued2018
dc.identifier.citationGuijo, M., Ceballos Chávez, M., Gómez Marín, E., Basurto Cayuela, L. y Reyes, J.C. (2018). Expression of TDRD9 in a subset of lung carcinomas by CpG island hypomethylation protects from DNA damage. Oncotarget, 9 (11), 9618-9631.
dc.identifier.issn1949-2553es
dc.identifier.urihttps://hdl.handle.net/11441/81581
dc.description.abstractTudor domain containing protein 9 (TDRD9) is a RNA helicase normally expressed in the germline, where it is involved in the biosynthesis of PIWI-interacting RNAs (piRNAs). Here, we show that TDRD9 is highly expressed in a subset of non-small cell lung carcinomas and derived cell lines by hypomethylation of its CpG island. Furthermore, TDRD9 expression is associated with poor prognosis in lung adenocarcinoma. We find that downregulation of TDRD9 expression in TDRD9-positive cell lines causes a decrease in cell proliferation, S-phase cell cycle arrest, and apoptosis. Transcriptomic analysis demonstrated that TDRD9 knockdown causes upregulation of cell cycle and DNA repair genes. We also observed that TDRD9 knockdown triggers activation of the catalytic subunit of the DNA dependent protein kinase (DNA-PKcs) and phosphorylation of H2A.X, which are indicative of an increase of DNA double strand breaks. TDRD9- silenced cells also presented aberrant mitosis and abnormal-shaped nuclei indicating defects in chromosomal segregation. Finally, TDRD9 silencing caused hypersensitivity to the replication stress inducer aphidicolin, while overexpression of the protein increased resistance to the drug, suggesting that TDRD9 protects from replicative stress to TDRD9-positive tumor cells. Thus, our results place TDRD9 as a marker for prognosis and as a potential therapeutic target in a subset of lung carcinomas.es
dc.description.sponsorshipMinisterio de Economía y Competitividad BFU2014-53543-Pes
dc.description.sponsorshipJunta de Andalucía BIO-321es
dc.description.sponsorshipUnión Eeuropea FEDERes
dc.formatapplication/pdfes
dc.language.isoenges
dc.publisherImpact Journalses
dc.relation.ispartofOncotarget, 9 (11), 9618-9631.
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectDNA methylationes
dc.subjectpiRNAes
dc.subjectDNA damagees
dc.subjectDNA-PKes
dc.subjectCánceres
dc.titleExpression of TDRD9 in a subset of lung carcinomas by CpG island hypomethylation protects from DNA damagees
dc.typeinfo:eu-repo/semantics/articlees
dcterms.identifierhttps://ror.org/03yxnpp24
dc.type.versioninfo:eu-repo/semantics/acceptedVersiones
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses
dc.relation.projectIDBFU2014-53543-Pes
dc.relation.projectIDBIO-321es
dc.relation.publisherversionhttps://doi.org/10.18632/oncotarget.22709es
dc.identifier.doi10.18632/oncotarget.22709es
idus.format.extent14 p.es
dc.journaltitleOncotargetes
dc.publication.volumen9es
dc.publication.issue11es
dc.publication.initialPage9618es
dc.publication.endPage9631es

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