Bromodomain-containing protein BRPF1 is a therapeutic target for liver cancer

• Published in: Communications biology Vol. 4; no. 1; pp. 888 - 14
• Main Authors: Cheng, Carol Lai-Hung, Tsang, Felice Hoi-Ching, Wei, Lai, Chen, Mengnuo, Chin, Don Wai-Ching, Shen, Jialing, Law, Cheuk-Ting, Lee, Derek, Wong, Carmen Chak-Lui, Ng, Irene Oi-Lin, Wong, Chun-Ming
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.07.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 38; 38/109; 38/91; 59/5; 631/337/176; 631/67/1504/1610/4029; 64/60; 82/80; Acetylation; Biology; Biomedical and Life Sciences; Cancer therapies; Cell cycle; Epigenetics; Hepatocellular carcinoma; Histones; Life Sciences; Liver cancer; Patients; Senescence; Therapeutic targets; Transcriptomes
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-021-02405-6

Epigenetic deregulation plays an essential role in hepatocellular carcinoma (HCC) progression. Bromodomains are epigenetic “readers” of histone acetylation. Recently, bromodomain inhibitors have exhibited promising therapeutic potential for cancer treatment. Using transcriptome sequencing, we identified BRPF1 (bromodomain and PHD finger containing 1) as the most significantly upregulated gene among the 43 bromodomain-containing genes in human HCC. BRPF1 upregulation was significantly associated with poor patient survival. Gene ablation or pharmacological inactivation of BRPF1 significantly attenuated HCC cell growth in vitro and in vivo. BRPF1 was involved in cell cycle progression, senescence and cancer stemness. Transcriptome sequencing revealed that BRPF1 is a master regulator controlling the expression of multiple key oncogenes, including E2F2 and EZH2 . We demonstrated that BRPF1 activated E2F2 and EZH2 expression by facilitating promoter H3K14 acetylation through MOZ/MORF complex. In conclusion, BRPF1 is frequently upregulated in human HCCs. Targeting BRPF1 may be an approach for HCC treatment. Cheng et al. suggest that BRPF1 plays an oncogenic role in hepatocellular carcinoma (HCC), by controlling histone acetylation in the promoter regions of E2F2 and EZH2 . Its high levels are correlated with poor survival in HCC patients, and targeting it might serve as a strategy for cancer treatment.