BRD4 interacts with PML/RARα in acute promyelocytic leukemia

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.

Keywords

BRD4 / PML/RARα / APL / interaction

References

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Acknowledgements

Our study was performed with the support of the National Natural Science Foundation of China (No. 81370655) and grants from the Ministry of Science and Technology of China (No. 2013CB966802). We also greatly appreciate the institutional supports from the Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, China.

Compliance with ethics guidelines

Qun Luo, Wanglong Deng, Haiwei Wang, Huiyong Fan, and Ji Zhang declare that they have no conflict of interest. This article does not contain any studies with human or animal subjects performed by any of the authors.

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