dc.creator | Guijo, Macarena | es |
dc.creator | Ceballos Chávez, María | es |
dc.creator | Gómez Marín, Elena | es |
dc.creator | Basurto Cayuela, Laura | es |
dc.creator | Reyes, José C. | es |
dc.date.accessioned | 2019-01-15T13:18:05Z | |
dc.date.available | 2019-01-15T13:18:05Z | |
dc.date.issued | 2018 | |
dc.identifier.citation | Guijo, 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.issn | 1949-2553 | es |
dc.identifier.uri | https://hdl.handle.net/11441/81581 | |
dc.description.abstract | Tudor 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.sponsorship | Ministerio de Economía y Competitividad BFU2014-53543-P | es |
dc.description.sponsorship | Junta de Andalucía BIO-321 | es |
dc.description.sponsorship | Unión Eeuropea FEDER | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | Impact Journals | es |
dc.relation.ispartof | Oncotarget, 9 (11), 9618-9631. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | DNA methylation | es |
dc.subject | piRNA | es |
dc.subject | DNA damage | es |
dc.subject | DNA-PK | es |
dc.subject | Cáncer | es |
dc.title | Expression of TDRD9 in a subset of lung carcinomas by CpG island hypomethylation protects from DNA damage | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/acceptedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.relation.projectID | BFU2014-53543-P | es |
dc.relation.projectID | BIO-321 | es |
dc.relation.publisherversion | https://doi.org/10.18632/oncotarget.22709 | es |
dc.identifier.doi | 10.18632/oncotarget.22709 | es |
idus.format.extent | 14 p. | es |
dc.journaltitle | Oncotarget | es |
dc.publication.volumen | 9 | es |
dc.publication.issue | 11 | es |
dc.publication.initialPage | 9618 | es |
dc.publication.endPage | 9631 | es |