Akira, YOROZU

Eiichiro, YAMAMOTO

Gouta, SUDO

Hajime, SASAKI

Hideki, WAKASUGI

Hiromu, SUZUKI

Hiroshi, KITAJIMA

Hiroshi, NAKASE

Kazuya, ISHIGURO

Masahiro, KAI

Noriyuki, AKUTU

Shigeru, SASAKI

Takeshi, NIINUMA

Tomo, HATAHIRA

Bromodomain and extra terminal (BET) family proteins, which include BRD4, are readers of histone acetyl-lysines and key regulators of gene transcription. BRD4 inhibitors exert anti-tumor effects in various cancers, including hepatocellular carcinoma (HCC). We investigated the mechanism underlying the antitumor effects of BRD4 inhibition in HCC. We first tested the effects of the BRD4 inhibitor JQ1 in a series of 9 HCC cell lines and found that it strongly suppressed HCC cell proliferation by inducing cell cycle arrest and apoptosis. Gene expression microarray analysis revealed that JQ1 also induced marked changes in the gene expression profiles of HCC cells, and genes associated with cell cycle and apoptosis were significantly enriched among the affected genes. Notably, a number of cancer-related genes, including BCAT1, DDR1, GDF15, FANCD2, SENP1 and TYRO3, were strongly suppressed by JQ1 in HCC cells. We also confirmed BRD4 bound within the promoter regions of these genes, which suggests they are targets of BRD4 in HCC cells. JQ1 thus appears to exert its anti-tumor effects in HCC by suppressing multiple BRD4 target genes

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Analysis of the anti-tumor mechanism of BRD4 inhibition in hepatocellular carcinoma

Analysis of the anti-tumor mechanism of BRD4 inhibition in hepatocellular carcinoma

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