Inhibition of BRD4 Suppresses the Growth of Esophageal Squamous Cell Carcinoma

Abstract

Background

Bromodomain-containing protein 4 (BRD4) binds acetylated lysine residues on histones to facilitate the epigenetic regulation of many genes, and it plays a key role in many cancer types. Despite many prior reports that have explored the importance of BRD4 in oncogenesis and the regulation of epigenetic memory, its role in esophageal squamous cell carcinoma (ESCC) progression is poorly understood. Here, we investigated BRD4 expression in human ESCC tissues to understand how it regulates the biology of these tumor cells.

Methods

BRD4 expression in ESCC tissues was measured via immunohistochemical staining. BRD4 inhibition in the Eca-109 and KYSE-150 ESCC cell lines was conducted to explore its functional role in these tumor cells.

Results

BRD4 overexpression was observed in ESCC tissues and cells, and inhibiting the function of the gene impaired the proliferative, invasive, and migratory activity of these cells while promoting their apoptosis. Cyclin D1 and c-Myc expression were also suppressed by BRD4 inhibition, and the expression of key epithelial-mesenchymal transition markers including E-cadherin and Vimentin was markedly altered by such inhibition.

Conclusions

BRD4 plays key functional roles in the biology of ESCC, proposing that it could be a viable therapeutic target for treating this cancer type.

Keywords:

• BRD4
• esophageal squamous cell carcinoma
• proliferation
• apoptosis
• epithelial-to-mesenchymal transition

Disclosure statement

All the authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Third Affiliated Hospital of Soochow University ethics committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All the patients gave their written informed consent.

Additional information

Funding

This work was supported by grants from the National Key R&D Plan (2018YFC1313400); the National Natural Science Foundation of China (31570877, 31570908, and 31729001); the National Key Technology R&D Program (2015BAI12B12); Jiangsu Engineering Research Center for Tumor Immunotherapy (BM2014404); the Key R&D Project of Science and Technology Department of Jiangsu Province (BE2018645 and BE2016660) and the Innovation and Entrepreneurship Talents Project of Longyuan Youth (2020RCXM127).