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http://hdl.handle.net/2445/123911
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DC Field | Value | Language |
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dc.contributor.author | Sharma, Varun K. | - |
dc.contributor.author | Raimondi, Vittoria | - |
dc.contributor.author | Ruggero, Katia | - |
dc.contributor.author | Pise-Masison, Cynthia A. | - |
dc.contributor.author | Cavallari, Ilaria | - |
dc.contributor.author | Silic-Benussi, Micol | - |
dc.contributor.author | Ciminale, Vincenzo | - |
dc.contributor.author | D'Agostino, Donna M. | - |
dc.date.accessioned | 2018-07-25T07:41:16Z | - |
dc.date.available | 2018-07-25T07:41:16Z | - |
dc.date.issued | 2018-05-04 | - |
dc.identifier.uri | http://hdl.handle.net/2445/123911 | - |
dc.description.abstract | Human T-lymphotropic virus 1 (HTLV-1) immortalizes T-cells and is the causative agent of adult T-cell leukemia/lymphoma (ATLL). HTLV-1 replication and transformation are governed by multiple interactions between viral regulatory proteins and host cell factors that remain to be fully elucidated. The present study investigated the impact of HTLV-1 infection on the expression of miR-34a, a microRNA whose expression is downregulated in many types of cancer. Results of RT-PCR assays showed that five out of six HTLV-1-positive cell lines expressed higher levels of miR-34a compared to normal PBMC or purified CD4+ T-cells. ATLL cell line ED, which did not express miR-34a, showed methylation of the miR-34a promoter. Newly infected PBMC and samples from 10 ATLL patients also showed a prominent increase in miR-34a expression compared to PBMC controls. The primary miR-34a transcript expressed in infected cell line C91PL contained binding motifs for NF-kappa B and p53. Pharmacological inhibition of NF-kappa B with Bay 11-7082 indicated that this pathway contributes to sustain miR-34a levels in infected cells. Treatment of infected cell lines with the p53 activator nutlin-3a resulted in a further increase in miR-34a levels, thus confirming it as a transcriptional target of p53. Nutlin-3a-treated cells showed downregulation of known miR-34a targets including the deacetylase SIRT1, which was accompanied by increased acetylation of p53, a substrate of SIRT1. Transfection of C91PL cells with a miR-34a mimic also led to downregulation of mRNA targets including SIRT1 as well as the pro-apoptotic factor BAX. Unlike nutlin-3a, the miR-34a mimic did not cause cell cycle arrest or reduce cell viability. On the other hand, sequestration of miR-34a with a sponge construct resulted in an increase in death of C91PL cells. These findings provide evidence for a functional role for miR-34a in fine-tuning the expression of target genes that influence the turnover of HTLV-1-infected cells. | - |
dc.format.extent | 15 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | Frontiers Media Sa | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.3389/fmicb.2018.00832 | - |
dc.relation.ispartof | Frontiers In Microbiology, 2018, Vol. 9, Article 832 | - |
dc.relation.uri | https://doi.org/10.3389/fmicb.2018.00832 | - |
dc.rights | cc-by (c) Sharma, Varun K. et al., 2018 | - |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.source | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) | - |
dc.subject.classification | Cèl·lules T | - |
dc.subject.classification | Expressió gènica | - |
dc.subject.classification | Càncer | - |
dc.subject.classification | Retrovirus | - |
dc.subject.other | T cells | - |
dc.subject.other | Gene expression | - |
dc.subject.other | Cancer | - |
dc.subject.other | Retroviruses | - |
dc.title | Expression Of Mir-34a In T-cells Infected By Human T-lymphotropic Virus 1 | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.date.updated | 2018-07-24T11:41:23Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 29780367 | - |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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SharmaVK.pdf | 2.46 MB | Adobe PDF | View/Open |
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