EP300通过SNAI2促进膀胱癌症细胞迁移
EP300 promotes bladder cancer cell migration through SNAI2.
摘要(中文译文)
EP300是膀胱癌中频繁突变的转录辅激活因子，已被证实与多种癌症的恶性程度呈正相关。高侵袭性膀胱癌通常与肌层浸润性进展相关，而这一过程与膀胱癌的上皮-间质转化（EMT）能力密切相关。本研究对根治性膀胱切除术获得的膀胱癌组织及癌旁正常组织进行免疫组化染色，以验证EP300与膀胱癌恶性程度之间的正相关性。我们观察到，EP300小分子抑制剂A485在划痕愈合实验和Transwell实验中均显著抑制多种膀胱癌细胞系（SW780、T24、RT4和5637）的细胞迁移。此外，利用类器官三维培养系统，A485破坏了T24细胞系中类器官间连接管状结构的形成，同时A485也破坏了SW780和5637细胞系中类器官从基质向非基质区域的迁移。在体内实验中，A485显示出抑制BBN诱导的小鼠膀胱癌侵袭的趋势。批量RNA测序分析显示，A485在多种膀胱癌细胞系中普遍下调SNAI2相关信号通路。此外，蛋白质印迹证实A485显著降低了T24和SW780细胞系中组蛋白H3第27位赖氨酸（H3K27ac）的全局乙酰化水平以及SNAI2的表达。事实上，Transwell实验显示SNAI2过表达增强了膀胱癌细胞的迁移能力。综上所述，我们的研究结果表明EP300通过上调SNAI2促进膀胱癌细胞迁移，靶向EP300可能是抑制膀胱癌侵袭过程的潜在治疗策略。
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.
如何引用
AMA
Qing Zhang, Chongjie He, Yingzhou Hong, Tao Huang, Shuangsheng Deng, Cheng Peng, et al. EP300 promotes bladder cancer cell migration through SNAI2.. PloS one. 2026; doi:10.1371/journal.pone.0347209.
APA
Qing Zhang, Chongjie He, Yingzhou Hong, Tao Huang, Shuangsheng Deng, Cheng Peng, et al (2026). EP300 promotes bladder cancer cell migration through SNAI2.. PloS one. https://doi.org/10.1371/journal.pone.0347209
GB/T 7714
Qing Zhang, Chongjie He, Yingzhou Hong, Tao Huang, Shuangsheng Deng, Cheng Peng, et al. EP300 promotes bladder cancer cell migration through SNAI2.[J]. PloS one, 2026 doi:10.1371/journal.pone.0347209.
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