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BRD4 interacts with PML/RARα in acute promyelocytic leukemia / 医学前沿
Frontiers of Medicine ; (4): 726-734, 2018.
Article in English | WPRIM | ID: wpr-771271
ABSTRACT
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.
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Full text: Available Index: WPRIM (Western Pacific) Main subject: Pharmacology / Azepines / Transcription Factors / Triazoles / RNA, Messenger / Nuclear Proteins / Tumor Cells, Cultured / Leukemia, Promyelocytic, Acute / Down-Regulation / Gene Expression Regulation, Neoplastic Limits: Humans Language: English Journal: Frontiers of Medicine Year: 2018 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Pharmacology / Azepines / Transcription Factors / Triazoles / RNA, Messenger / Nuclear Proteins / Tumor Cells, Cultured / Leukemia, Promyelocytic, Acute / Down-Regulation / Gene Expression Regulation, Neoplastic Limits: Humans Language: English Journal: Frontiers of Medicine Year: 2018 Type: Article