期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 511, 期 1, 页码 35-40出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2019.01.087
关键词
E2F5; MYCN; Neuroblastoma cells; Proliferation; Cyclin-dependent kinase; Cell cycle progression
The MYCN oncoprotein induces the proliferation of neuroblastoma cells through regulating gene transcription. The E2F transcription factor 5 (E2F5) plays an oncogenic role in several types of cancer, however, its role in neuroblastoma cells remains poorly characterized. We report here that MYCN positively regulates E2F5 expression in neuroblastoma cells. Analyses of chromatin immunoprecipitation (ChIP) and reporter gene assay demonstrate that MYCN directly binds to a Myc E-Box DNA binding motif within the promoter of E2F5 gene, whereby inducing its transcription. In addition, E2F5 knockdown inhibits the proliferation of MYCN-amplified neuroblastoma cells. Furthermore, E2F5 knockdown inhibits cell cycle progression, which could be attributed to its regulation in the expression of related cyclindependent kinases (CDKs), including CDK2 and CDK6. These results suggest that MYCN-regulated E2F5 upregulation is an important mechanism through which MYCN induces the proliferation of neuroblastoma cells. In conclusion, this study identifies E2F5 as a pro-proliferative factor in MYCN-amplified neuroblastoma cells, and also implicates it as a potential target in neuroblastoma treatment. (C) 2019 Published by Elsevier Inc.
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