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J Cell Mol Med ; 22(5): 2612-2621, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29512921

RESUMEN

DHX15 plays a role in leukaemogenesis and leukaemia relapse. However, the mechanism underlying the transcriptional regulation of DHX15 in ALL has not been elucidated. Our present study aimed to explore the functional promoter region of DHX15 and to investigate the transcription factors controlling the transcription of this gene. A luciferase assay performed with several truncated constructs identified a 501-bp region as the core promoter region of DHX15. Site-directed mutagenesis, electrophoretic mobility shift and chromatin immunoprecipitation assays showed that ETS1 and SP1 occupied the DHX15 promoter. Furthermore, knockdown of ETS1 and SP1 resulted in suppression of DHX15, whereas the overexpression of these genes led to up-regulation of DHX15. Interestingly, in samples obtained from patients with ALL at diagnosis, both ETS1 and SP1 correlated positively with DHX15 expression. Additionally, differences in methylation of the DHX15 core promoter region were not observed between the patients and controls. In conclusion, we identified the core promoter region of DHX15 and demonstrated that ETS1 and SP1 regulated DHX15 expression in ALL.


Asunto(s)
Regulación Leucémica de la Expresión Génica , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteína Proto-Oncogénica c-ets-1/metabolismo , ARN Helicasas/genética , Factor de Transcripción Sp1/metabolismo , Emparejamiento Base/genética , Secuencia de Bases , Sitios de Unión , Línea Celular Tumoral , Islas de CpG/genética , Metilación de ADN/genética , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/patología , Regiones Promotoras Genéticas , Unión Proteica , Proteína Proto-Oncogénica c-ets-1/genética , ARN Helicasas/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Sitio de Iniciación de la Transcripción , Transcripción Genética
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