EP300 promotes bladder cancer cell migration through SNAI2

Sep 22, 2026

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EP300, a frequently mutated transcriptional coactivator in bladder cancer, correlates with malignancy and aggressive muscle-invasive progression linked to epithelial-mesenchymal transition (EMT). Immunohistochemistry validated EP300 association in radical cystectomy tissues. The EP300 inhibitor A485 suppressed migration in multiple bladder cancer cell lines via scratch wound healing and Transwell assays, disrupted organoid interconnections and migration, and reduced BBN-induced invasion trend in mice. Bulk RNAseq and western blotting showed A485 downregulated SNAI2 pathways and decreased H3K27ac and SNAI2; SNAI2 overexpression enhanced migration, supporting EP300-SNAI2 as a therapeutic target.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages15

Reading Time38 min

AccessFree to download

Abstract

Introduction

Materials and Methods

Results

Discussion

OPEN ACCESS Citation: Zhang Q, He C, Hong Y, Huang T, Deng S, Peng C, et al. (2026) EP300 promotes bladder cancer cell migration through SNAI2 . PLoS One 21(6): e0347209. [https://doi](https://doi). org/10.1371/journal.pone.0347209 Editor: Habib Boukerche,“INSERM”, FRANCE Received: May 5, 2025 Accepted: March 30, 2026 Published: June 8, 2026 Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: [https://doi.org/10.1371/journal](https://doi.org/10.1371/journal). pone.0347209 Copyright: © 2026 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. RESEARCH ARTICLE EP300 promotes bladder cancer cell migration through SNAI2 Qing Zhang1,2, Chongjie He1, Yingzhou Hong1, Tao Huang1, Shuangsheng Deng1, Cheng Peng1, Haifeng Wang2, Chunming Guo1* 1 Yunnan Key Laboratory of Cell Metabolism and Disease, Center for Life Sciences, School of Life Sciences, Yunnan University, Kunming, China, 2 Department of Urology, The Second Affiliated Hospital of Kunming Medical University, Kunming, China * [chunmingguo@ynu.edu.cn](chunmingguo@ynu.edu.cn) Abstract EP300, a frequently mutated transcriptional coactivator in bladder cancer, has been demonstrated to positively correlate with malignancy in various cancers. Highly aggressive bladder cancers are often associated with muscle-invasive progression, a process closely linked to the epithelial-mesenchymal transition (EMT) capability of bladder cancer. Here, we performed immunohistochemical staining on bladder cancer tissues and adjacent normal tissues obtained from radical cystectomy to validate the positive association between EP300 and bladder cancer malignancy. We observed that A485, a small-molecule inhibitor of EP300, significantly inhibited cell migration in multiple bladder cancer cell lines (SW780, T24, RT4 and 5637) both in scratch wound healing and Transwell assays. Additionally, take the advantage of organoid-3D culture system, A485 disrupted the formation of inter-organoids connecting tubular structures in T24 cell line, while A485 also disrupted the organoid migration from matrix out-toward the non-matrix region both in SW780 and 5637 cell lines. In in vivo experiment, A485 showed a trend toward inhibiting BBN-induced bladder cancer invasion in mice. Bulk RNAseq analysis revealed that A485 commonly downregulated SNAI2-related signaling pathways across multiple bladder cancer cell lines. Furthermore, western blotting confirmed that A485 significantly reduced the global level of acetylation of histone H3 at lysine 27 (H3K27ac) as well as SNAI2 expression in T24 and SW780 cell lines. Indeed, overexpression of SNAI2 enhanced the migratory capacity of bladder cancer cells via Transwell assay. Collectively, our findings demonstrate that EP300 promoted bladder cancer cell migration via up-regulating SNAI2, targeting EP300 could be a potential therapeutic strategy to inhibit the process of bladder cancer invasion. Introduction Bladder cancer, particularly muscle-invasive bladder cancer (MIBC), remains a significant clinical challenge due to its high-grade metastatic character, and resistance PLOS One | [https://doi.org/10.1371/journal.pone.0347209](https://doi.org/10.1371/journal.pone.0347209) June 8, 2026 1 / 15 Data availability statement: The data used in this study are available from the GSA database ([https://ngdc.cncb.ac.cn/](https://ngdc.cncb.ac.cn/)) with accession number PRJCA038992 and at the following links: [https://ngdc.cncb.ac.cn/gsa-hu](https://ngdc.cncb.ac.cn/gsa-hu)man/s/aRI60rR2 [https://ngdc.cncb.ac.cn/](https://ngdc.cncb.ac.cn/

FAQs

What is the central finding about EP300 in bladder cancer?

EP300 promotes bladder cancer cell migration by upregulating SNAI2, linking EP300 activity to invasive behavior.

How does A485 affect bladder cancer cell migration?

A485 significantly inhibits migration across multiple bladder cancer cell lines in scratch wound healing and Transwell assays.

What evidence links SNAI2 to the migration effects?

A485 downregulated SNAI2-related signaling pathways and reduced SNAI2 protein levels; SNAI2 overexpression increased migratory capacity in Transwell assays.

Sep 22, 2026

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