Bromodomain-containing Protein BRPF1 is a Therapeutic Target for Liver Cancer

Overview

Journal Commun Biol

Specialty Biology

Date 2021 Jul 21

PMID 34285329

Citations 15

Authors

Carol Lai-Hung Cheng

Felice Hoi-Ching Tsang

Lai Wei

Mengnuo Chen

Don Wai-Ching Chin

Jialing Shen

Cheuk-Ting Law

Derek Lee

Carmen Chak-Lui Wong

Irene Oi-Lin Ng

Chun-Ming Wong

Affiliations

Soon will be listed here.

Abstract

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.

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