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Campo DC | Valor | Lengua/Idioma |
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dc.contributor.author | Rauschert, Inés | - |
dc.contributor.author | Aldunate Caramori, Fabián | - |
dc.contributor.author | Preussner, J. | - |
dc.contributor.author | Arocena-Sutz, Germán Miguel | - |
dc.contributor.author | Peraza Geist, Vanina Mercedes | - |
dc.contributor.author | Looso, M. | - |
dc.contributor.author | Benech, Juan Claudio | - |
dc.contributor.author | Agrelo, Ruben | - |
dc.date.accessioned | 2019-11-26T18:14:56Z | - |
dc.date.available | 2019-11-26T18:14:56Z | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | Rauschert, I., Aldunate, F., Preussner, J. y otros. "Promoter hypermethylation as a mechanism for Lamin A/C silencing in a subset of neuroblastoma cells". PLoS ONE [en línea]. 2017 12 (4), art. no. e0175953. doi: 10.1371/journal.pone.0175953 | es |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | https://hdl.handle.net/20.500.12008/22555 | - |
dc.description.abstract | Nuclear lamins support the nuclear envelope and provide anchorage sites for chromatin. They are involved in DNA synthesis, transcription, and replication. It has previously been reported that the lack of Lamin A/C expression in lymphoma and leukaemia is due to CpG island promoter hypermethylation. Here, we provide evidence that Lamin A/C is silenced via this mechanism in a subset of neuroblastoma cells. Moreover, Lamin A/C expression can be restored with a demethylating agent. Importantly, Lamin A/C reintroduction reduced cell growth kinetics and impaired migration, invasion, and anchorage-independent cell growth. Cytoskeletal restructuring was also induced. In addition, the introduction of lamin Δ50, known as Progerin, caused senescence in these neuroblastoma cells. These cells were stiffer and developed a cytoskeletal structure that differed from that observed upon Lamin A/C introduction. Of relevance, short hairpin RNA Lamin A/C depletion in unmethylated neuroblastoma cells enhanced the aforementioned tumour properties. A cytoskeletal structure similar to that observed in methylated cells was induced. Furthermore, atomic force microscopy revealed that Lamin A/C knockdown decreased cellular stiffness in the lamellar region. Finally, the bioinformatic analysis of a set of methylation arrays of neuroblastoma primary tumours showed that a group of patients (around 3%) gives a methylation signal in some of the CpG sites located within the Lamin A/C promoter region analysed by bisulphite sequencing PCR. These findings highlight the importance of Lamin A/C epigenetic inactivation for a subset of neuroblastomas, leading to enhanced tumour properties and cytoskeletal changes. Additionally, these findings may have treatment implications because tumour cells lacking Lamin A/C exhibit more aggressive behaviour. | es |
dc.format.extent | 31 h. | es |
dc.format.mimetype | application/pdf | es |
dc.language.iso | en | es |
dc.publisher | PLoS | es |
dc.relation.ispartof | PLoS ONE, 2017 12 (4), art. no. e0175953 | es |
dc.rights | Las obras depositadas en el Repositorio se rigen por la Ordenanza de los Derechos de la Propiedad Intelectual de la Universidad de la República.(Res. Nº 91 de C.D.C. de 8/III/1994 – D.O. 7/IV/1994) y por la Ordenanza del Repositorio Abierto de la Universidad de la República (Res. Nº 16 de C.D.C. de 07/10/2014) | es |
dc.subject | Lamin Type A | es |
dc.subject | Lamins | es |
dc.subject | Syndrome HGPS | es |
dc.title | Promoter hypermethylation as a mechanism for Lamin A/C silencing in a subset of neuroblastoma cells | es |
dc.type | Artículo | es |
dc.contributor.filiacion | Rauschert Inés, IIBCE | - |
dc.contributor.filiacion | Aldunate Caramori Fabián, Universidad de la República (Uruguay). Facultad de Ciencias. Centro de Investigaciones Nucleares | - |
dc.contributor.filiacion | Preussner J. | - |
dc.contributor.filiacion | Arocena-Sutz Miguel, Instituto Pasteur (Montevideo) | - |
dc.contributor.filiacion | Peraza Geist Vanina Mercedes, Instituto Pasteur (Montevideo) | - |
dc.contributor.filiacion | Looso M. | - |
dc.contributor.filiacion | Benech Juan C., IIBCE | - |
dc.contributor.filiacion | Agrelo Ruben, Instituto Pasteur (Montevideo) | - |
dc.rights.licence | Licencia Creative Commons Atribución (CC - By 4.0) | es |
dc.identifier.doi | 10.1371/journal.pone.0175953 | - |
Aparece en las colecciones: | Publicaciones académicas y científicas - Facultad de Ciencias |
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101371journalpone0175953.pdf | 7,47 MB | Adobe PDF | Visualizar/Abrir |
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