MDS1 和 EVI1 复合基因座 (MECOM) 是一种编码多种变体的转录因子，与卵巢癌的进展有关。卵巢癌中调节区调节 MECOM 表达的功能尚不完全清楚。在这项研究中，在用溴结构域和末端外 (BET) 抑制剂 JQ-1 处理的卵巢癌细胞系中评估了 MECOM 表达。使用 CCK-8、集落形成、伤口愈合和 Transwell 分析来分析致癌表型。在稳定的 sgRNA 转染的 OVCAR3 细胞系中评估了致癌表型。通过皮下注射增强子删除的 OVCAR3 细胞系来测定异种移植小鼠模型。结果显示，JQ-1处理的细胞系中MECOM的表达下调。已发表的 3 个卵巢癌细胞系 ChIP 测序 (H3K27Ac) 数据显示第一个外显子周围存在潜在的增强子。删除 MECOM 增强子后，OVCAR3 细胞中 mRNA 和蛋白表达下调。同样，细胞和异种移植小鼠模型中的致癌表型均显着减弱。本研究表明JQ-1可以抑制MECOM的表达和肿瘤发生。 MECOM 增强子活性的删除在抑制卵巢癌进展中具有不可或缺的作用，这为通过应用这种非编码 DNA 删除来治疗卵巢癌提供了一个有希望的机会。© 2024。作者，独家许可给 Springer-Verlag GmbH 德国（施普林格自然的一部分）。

MDS1 and EVI1 complex locus (MECOM), a transcription factor encoding several variants, has been implicated in progression of ovarian cancer. The function of regulatory regions in regulating MECOM expression in ovarian cancer is not fully understood. In this study, MECOM expression was evaluated in ovarian cancer cell lines treated with bromodomain and extraterminal (BET) inhibitor JQ-1. Oncogenic phenotypes were assayed using assays of CCK-8, colony formation, wound-healing and transwell. Oncogenic phenotypes were estimated in stable sgRNA-transfected OVCAR3 cell lines. Xenograft mouse model was assayed via subcutaneous injection of enhancer-deleted OVCAR3 cell lines. The results displayed that expression of MECOM is downregulated in cell lines treated with JQ-1. Data from published ChIP-sequencing (H3K27Ac) in 3 ovarian cancer cell lines displayed a potential enhancer around the first exon. mRNA and protein expression were downregulated in OVCAR3 cells after deletion of the MECOM enhancer. Similarly, oncogenic phenotypes both in cells and in the xenograft mouse model were significantly attenuated. This study demonstrates that JQ-1 can inhibit the expression of MECOM and tumorigenesis. Deletion of the enhancer activity of MECOM has an indispensable role in inhibiting ovarian cancer progress, which sheds light on a promising opportunity for ovarian cancer treatment through the application of this non-coding DNA deletion.© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.