دورية أكاديمية
RNA-Seq reveals the existence of a CDKN1C-E2F1-TP53 axis that is altered in human T-cell lymphoblastic lymphomas
| العنوان: | RNA-Seq reveals the existence of a CDKN1C-E2F1-TP53 axis that is altered in human T-cell lymphoblastic lymphomas |
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| المؤلفون: | López-Nieva, Pilar, Fernández-Navarro, Pablo, Vaquero-Lorenzo, Concepción, Villa-Morales, María, Graña-Castro, Osvaldo, Cobos Fernández, María Ángeles, López-Lorenzo, José Luis, Llamas, Pilar, González-Sánchez, Laura, Sastre, Isabel, Pollan, Marina, Malumbres, Marcos, Santos, Javier, Fernández-Piqueras, José |
| المساهمون: | UAM. Departamento de Biología, UAM. Departamento de Medicina Preventiva y Salud Pública y Microbiología, Centro de Biología Molecular Severo Ochoa (CBM), Instituto de Investigación Sanitaria Fundación Jiménez Díaz (IIS-FJD) |
| بيانات النشر: | BioMed Central |
| سنة النشر: | 2018 |
| المجموعة: | Universidad Autónoma de Madrid (UAM): Biblos-e Archivo |
| مصطلحات موضوعية: | CDKN1C-E2F1-TP53 deregulation, Deregulation of miRNAs, Promoter hypermethylation, T-cell lymphoblastic lymphoma, Biología y Biomedicina / Biología |
| الوصف: | Background: Precursor T-cell lymphoblastic lymphomas (T-LBL) are rare aggressive hematological malignancies that mainly develop in children. As in other cancers, the loss of cell cycle control plays a prominent role in the pathogenesis in these malignancies that is primarily attributed to loss of CDKN2A (encoding protein p16INK4A). However, the impact of the deregulation of other genes such as CDKN1C, E2F1, and TP53 remains to be clarified. Interestingly, experiments in mouse models have proven that conditional T-cell specific deletion of Cdkn1c gene may induce a differentiation block at the DN3 to DN4 transition, and that the loss of this gene in the absence of Tp53 led to aggressive thymic lymphomas. Results: In this manuscript, we demonstrated that the simultaneous deregulation of CDKN1C, E2F1, and TP53 genes by epigenetic mechanisms and/or the deregulation of specific microRNAs, together with additional impairing of TP53 function by the expression of dominant-negative isoforms are common features in primary human T-LBLs. Conclusions: Previous experimental work in mice revealed that T-cell specific deletion of Cdkn1c accelerates lymphomagenesis in the absence of Tp53. If, as expected, the consequences of the deregulation of the CDKN1C-E2F1-TP53 axis were the same as those experimentally demonstrated in mouse models, the disruption of this axis might be useful to predict tumor aggressiveness, and to provide the basis towards the development of potential therapeutic strategiesin human T-LBL ; The authors would like to thank the Spanish Ministry of Economy and Competitiveness (SAF2015–70561-R; MINECO/FEDER, EU) and the Autonomous Community of Madrid, Spain (B2017/BMD-3778; LINFOMAS-CM) for funding this work. Institutional grants from the Fundación Ramón Areces and Banco de Santander are also acknowledged |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1471-2407 |
| العلاقة: | BMC Cancer; https://doi.org/10.1186/s12885-018-4304-yTest; Gobierno de España. SAF2015–70561-R; Comunidad de Madrid. B2017/BMD-3778/LINFOMAS; BMC Cancer 18.1 (2018): 430; http://hdl.handle.net/10486/683392Test; 430-1; 430-12; 18 |
| DOI: | 10.1186/s12885-018-4304-y |
| الإتاحة: | https://doi.org/10.1186/s12885-018-4304-yTest http://hdl.handle.net/10486/683392Test |
| حقوق: | © 2018 The Author(s) ; Reconocimiento ; openAccess |
| رقم الانضمام: | edsbas.C86FBCFF |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 14712407 |
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| DOI: | 10.1186/s12885-018-4304-y |