文章标题：EP300 promotes cervical cancer progression through a Wnt/β-catenin–dependent HIF-1α signaling axis
作者列表：Yue Zhang, Yongxin Zhang, Ke Wang
期刊：TOXICOLOGY AND APPLIED PHARMACOLOGY
发表时间：2026-1-19
影响因子：3.4
DOI:10.1016/j.taap.2026.117718
主要研究成果：Abstract
This study aimed to investigate the role of EP300 in cervical cancer progression, focusing on its functional effects related to pyroptosis under Wnt/β-catenin–dependent conditions. In SiHa and HeLa cells, EP300 was silenced using lentiviral-mediated knockdown under hypoxic conditions, and subsequent changes in cell proliferation, inflammatory cytokine secretion, and pyroptosis-related protein expression were evaluated. A subcutaneous HeLa xenograft model was established to examine the in vivo effects. Hypoxia-inducible factor 1-alpha (HIF-1α) expression was also analyzed. The results showed that hypoxia significantly increased the expression levels of EP300, β-catenin, and HIF-1α. EP300 knockdown was associated with decreased Wnt/β-catenin signaling and, under Wnt/β-catenin–dependent conditions, resulted in reduced HIF-1α expression and enhanced pyroptosis-related phenotypes. Activation of Wnt/β-catenin signaling by HLY78 partially reversed these alterations. In vivo, silencing EP300 suppressed tumor growth, decreased Ki67 expression, and increased pyroptosis markers, while activation of the Wnt/β-catenin pathway partially restored proliferation and reduced pyroptosis. Taken together, loss of EP300 function impedes cervical cancer progression by affecting the Wnt/β-catenin signaling axis and inducing concomitant changes in HIF-1α expression. This study provides functional evidence supporting the role of EP300 in the progression of cervical cancer under hypoxic conditions.
