Inhibition of BRD4 promotes migration of esophageal squamous cell carcinoma cells with low ACC1 expression.
10.12122/j.issn.1673-4254.2025.10.22
- Author:
Wenxin JIA
1
;
Shuhua HUO
1
;
Jiaping TANG
1
;
Yuzhen LIU
1
;
Baosheng ZHAO
1
Author Information
1. Department of Thoracic Surgery, The First Affiliated Hospital of Henan Medical University, Weihui 453100, China.
- Publication Type:Journal Article
- Keywords:
BRD4;
acetyl-CoA carboxylase 1;
esophageal squamous cell carcinoma;
migration
- MeSH:
Humans;
Cell Movement;
Transcription Factors/metabolism*;
Esophageal Neoplasms/metabolism*;
Cell Line, Tumor;
Cell Cycle Proteins;
Azepines/pharmacology*;
Epithelial-Mesenchymal Transition;
Carcinoma, Squamous Cell/metabolism*;
Esophageal Squamous Cell Carcinoma;
Triazoles/pharmacology*;
Nuclear Proteins/genetics*;
Cell Proliferation;
Acetyl-CoA Carboxylase/genetics*;
Transfection;
Autophagy;
Bromodomain Containing Proteins
- From:
Journal of Southern Medical University
2025;45(10):2258-2269
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVES:To investigate the effect of BRD4 inhibition on migration of esophageal squamous cell carcinoma (ESCC) cells with low acetyl-CoA carboxylase 1 (ACC1) expression.
METHODS:ESCC cell lines with lentivirus-mediated ACC1 knockdown or transfected with a negative control sequence (shNC) were treated with DMSO, JQ1 (a BRD4 inhibitor), co-transfection with shNC-siBRD4 or siNC with additional DMSO or C646 (an ahistone acetyltransferase inhibitor) treatment, or JQ1combined with 3-MA (an autophagy inhibitor). BRD4 mRNA expression in the cells was detected using RT-qPCR. The changes in cell proliferation, migration, autophagy, and epithelial-mesenchymal transition (EMT) were examined with CCK8 assay, Transwell migration assay, and Western blotting.
RESULTS:ACC1 knockdown did not significantly affect BRD4 expression in the cells but obviously increased their sensitivity to JQ1. JQ1 treatment at 1 and 2 μmol/L significantly inhibited ESCC cell proliferation, while JQ1 at 0.2 and 2 μmol/L promoted cell migration. The cells with ACC1 knockdown and JQ1 treatment showed increased expresisons of vimentin and Slug and decreased expression of E-cadherin. BRD4 knockdown promoted migration of ESCC cells, and co-transfection with shACC1 and siBRD4 resulted in increased vimentin and Slug expressions and decreased E-cadherin expression in the cells. C646 treatment of the co-transfected cells reduced acetylation levels, decreased vimentin and Slug expressions, and increased E-cadherin expression. Treatment with JQ1 alone obviously increased LC3A/B-II levels in the cells either with or without ACC1 knockdown. In the cells with ACC1 knockdown and JQ1 treatment, additional 3-MA treatment significantly decreased the expressions of vimentin, Slug and LC3A/B-II and increased the expression of E-cadherin.
CONCLUSIONS:BRD4 inhibition promotes autophagy of ESCC cells via a histone acetylation-dependent mechanism, thereby enhancing EMT and ultimately increasing cell migration driven by ACC1 deficiency.
