基因敲除
细胞生长
癌症研究
A431电池
细胞周期
癌基因
细胞培养
BRD4
细胞凋亡
生物
溴尿嘧啶
细胞周期蛋白D1
分子生物学
细胞生物学
化学
表观遗传学
生物化学
基因
遗传学
作者
Tie Xiang,Jinyu Bai,Chang She,Daojiang Yu,Xiaozhong Zhou,Tianlan Zhao
标识
DOI:10.1016/j.cellsig.2017.10.010
摘要
The present study examined the expression and biological functions of bromodomain-containing protein 4 (BRD4) in skin squamous cell carcinoma (SCC) cells. Our results show that BRD4 mRNA and protein expression was upregulated in human skin SCC cells, as compared to its level in the normal skin keratinocytes and fibroblasts. Treatment with BRD4 inhibitors, JQ1 and CPI203, resulted in proliferation inhibition, apoptosis and cell cycle arrest in both established (A431 cell line) and primary skin SCC cells. Furthermore, BRD4 knockdown (by targeted shRNAs) or knockout (by CRISPR/Cas9) largely inhibited A431 cell proliferation. Reversely, forced-overexpression of BRD4 in A431 cells facilitated cell proliferation. We show that BRD4 is required for the expression of several oncogenes, including cyclin D1, Bcl-2 and MYC. BRD4 inhibition, knockdown or knockout significantly decreased above oncogene expression in SCC cells. In vivo, CRISPR/Cas9-mediated BRD4 knockout significantly suppressed A431 xenograft tumor growth in severe combined immunodeficient (SCID) mice. Together, our results suggest that BRD4 could be a novel and pivotal oncogenic protein of skin SCC.
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