Work

BRD4 Induces Esophageal Squamous Cell Carcinoma Progression via the Wnt/β-catenin Pathway

Year: 2025

Type: article

Abstract: BRD4, part of the bromodomain and extra terminal domain (BET) protein family, plays a pivotal role in gene transcription, DNA replication, and repair via transcription regulators. Despite its established involvement in various human diseases, its function in esophageal squamous cell carcinoma (ESCC) has not been fully explored. Our research investigated the association of BRD4 in ESCC and its underlying molecular mechanisms. The findings revealed that BRD4 knockdown notably diminished the cells' proliferation, migration, invasion capabilities and induced apoptosis and cell cycle arrest. Conversely, overexpression of BRD4 can reverse these phenotypes. Pearson correlation and enrichment analyses indicated that BRD4 expression was associated with the cell cycle and Wnt/β-catenin signaling pathway. Further validation confirmed that reduced BRD4 expression downregulates Cyclin D1 and c-Myc, and suppresses epithelial-to-mesenchymal transition (EMT) and Wnt/β-catenin signaling pathway. Furthermore, rescue experiments showed that overexpressing c-Myc significantly mitigated the inhibitory impact of BRD4. Moreover, by employing single-cell transcriptome sequencing, we explored the impact of the tumor microenvironment on BRD4 overexpression in ESCC cells. These insights confirmed BRD4's potential as a therapeutic target, suggesting that modulating its expression could yield promising strategies for ESCC treatment.

Source: Biochemical Genetics

DOI: 10.1007/s10528-025-11043-0