dc.contributor.author | Ramírez Moya, Julia | |
dc.contributor.author | Wert Lamas, León | |
dc.contributor.author | Riesco Eizaguirre, Garcilaso | |
dc.contributor.author | Santisteban, Pilar | |
dc.date.accessioned | 2019-11-04T10:05:07Z | |
dc.date.available | 2019-11-04T10:05:07Z | |
dc.date.issued | 2019 | |
dc.identifier.issn | 0950-9232 | spa |
dc.identifier.uri | http://hdl.handle.net/10641/1711 | |
dc.description.abstract | The global downregulation of microRNAs (miRNAs) is emerging as a common hallmark of cancer. However, the
mechanisms underlying this phenomenon are not well known. We identified that the oncogenic miR-146b-5p attenuates
miRNA biosynthesis by targeting DICER1 and reducing its expression. DICER1 overexpression inhibited all the miR-146binduced
aggressive phenotypes in thyroid cells. Systemic injection of an anti-miR-146b in mice with orthotopic thyroid
tumors suppressed tumor growth and recovered DICER1 levels. Notably, DICER1 downregulation promoted proliferation,
migration, invasion, and epithelial-mesenchymal transition through miRNA downregulation. Our analysis of The Cancer
Genome Atlas revealed a general decrease in DICER1 expression in thyroid cancer that was associated with a worse clinical
outcome. Administration of the small-molecule enoxacin to promote DICER1 complex activity reduced tumor
aggressiveness both in vitro and in vivo. Overall, our data confirm DICER1 as a tumor suppressor and show that
oncogenic miR-146b contributes to its downregulation. Moreover, our results highlight a potential therapeutic application of
RNA-based therapies including miRNA inhibitors and restoration of the biogenesis machinery, which may provide
treatments for thyroid and other cancers. | spa |
dc.language.iso | eng | spa |
dc.publisher | Oncogene | spa |
dc.rights | Atribución-NoComercial-SinDerivadas 3.0 España | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/3.0/es/ | * |
dc.title | Impaired microRNA processing by DICER1 downregulation endows thyroid cancer with increased aggressiveness. | spa |
dc.type | journal article | spa |
dc.type.hasVersion | AM | spa |
dc.rights.accessRights | open access | spa |
dc.description.extent | 3221 KB | spa |
dc.identifier.doi | 10.1038/s41388-019-0804-8 | spa |
dc.relation.publisherversion | https://www.nature.com/articles/s41388-019-0804-8 | spa |