RESUMEN
Bromodomain-containing 4 (BRD4) has been considered as an important requirement for disease maintenance and an attractive therapeutic target for cancer therapy. This protein can be targeted by JQ1, a selective small-molecule inhibitor. However, few studies have investigated whether BRD4 influenced acute promyelocytic leukemia (APL), and whether BRD4 had interaction with promyelocytic leukemia-retinoic acid receptor α (PML/RARα) fusion protein to some extent. Results from cell viability assay, cell cycle analysis, and Annexin-V/PI analysis indicated that JQ1 inhibited the growth of NB4 cells, an APL-derived cell line, and induced NB4 cell cycle arrest at G1 and apoptosis. Then, we used co-immunoprecipitation (co-IP) assay and immunoblot to demonstrate the endogenous interaction of BRD4 and PML/RARα in NB4 cells. Moreover, downregulation of PML/RARα at the mRNA and protein levels was observed upon JQ1 treatment. Furthermore, results from the RT-qPCR, ChIP-qPCR, and re-ChIP-qPCR assays showed that BRD4 and PML/RARα co-existed on the same regulatory regions of their target genes. Hence, we showed a new discovery of the interaction of BRD4 and PML/RARα, as well as the decline of PML/RARα expression, under JQ1 treatment.
Asunto(s)
Humanos , Apoptosis , Azepinas , Farmacología , Diferenciación Celular , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Leucemia Promielocítica Aguda , Quimioterapia , Genética , Proteínas Nucleares , Genética , Proteína de la Leucemia Promielocítica , Genética , ARN Mensajero , Genética , Receptor alfa de Ácido Retinoico , Genética , Factores de Transcripción , Genética , Triazoles , Farmacología , Células Tumorales CultivadasRESUMEN
Objective To analyze the differential gene expression between thymic carcinoids and normal thymic tissues and to study thepathogenesisofectopicACTH syndrome caused by thymic carcinoids. Methods Using gene chip technique, the gene differential expression of 2 tissues were observed following RNA labeled with different fluorescences (Cy3 and Cy5) hybridized to gene chip. Results Among 4224 genes on gene chip, 394 were up regulated more than 2 folds in thymic carcinoid tissues, 23 of which were associated with cell mitosis; 51 genes were upregulated more than 5 folds, 1 of which (PAK3) was associated with cell mitosis. Conclusion A group of differentially expressed genes were observed between the thymic carcinoids and normal thymic tissues.These overexpressed and cell mitosis-associated genes probably play a role in the pathogenesis of thymic carcinoid tumors.