The BRD4 Inhibitor JQ1 Suppresses Tumor Growth by Reducing C-Myc Expression in Endometrial Cancer

Overview

Journal J Transl Med

Publisher Biomed Central

Specialties Biomedical Engineering
General Medicine

Date 2022 Jul 28

PMID 35902869

Authors

Yingxin Pang

Gaigai Bai

Jing Zhao

Xuan Wei

Rui Li

Jie Li

Shunxue Hu

Lu Peng

Peishu Liu

Hongluan Mao

Affiliations

Soon will be listed here.

Abstract

Background: Endometrial cancer (EC) is the most common gynecological malignancy in developed countries. Efficacy of the bromodomain 4 (BRD4) inhibitor JQ1 has been reported for the treatment of various human cancers, but its potential impact on EC remains unclear. We therefore aimed to elucidate the function of BRD4 and the effects of JQ1 in EC in vivo and in vitro.

Methods: The mRNA expression of BRD4 was evaluated using datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). BRD4 protein expression in EC tissues was measured using immunohistochemistry (IHC) assays. The effects of JQ1 on EC were determined by using MTT and colony formation assays, flow cytometry and xenograft mouse models. The underlying mechanism was also examined by western blot and small interfering RNA (siRNA) transfection.

Results: BRD4 was overexpressed in EC tissues, and the level of BRD4 expression was strongly related to poor prognosis. The BRD4-specific inhibitor JQ1 suppressed cell proliferation and colony formation and triggered cell apoptosis, cell cycle arrest, and changes in the expression of proteins in related signaling pathways. Moreover, JQ1 decreased the protein expression of BRD4 and c-Myc, and knockdown of BRD4 or c-Myc reduced the viability of EC cells. Intraperitoneal administration of JQ1 (50 mg/kg) significantly suppressed the tumorigenicity of EC cells in a xenograft mouse model.

Conclusion: Our results demonstrate that BRD4 is a potential marker of EC and that the BRD4 inhibitor JQ1 is a promising chemotherapeutic agent for the treatment of EC.

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