目的 探究连接桥粒斑珠蛋白（JUP）通过结合SET结构域分支型蛋白1（SETDB1）抑制高级别浆液性卵巢癌（HGSOC）增殖、侵袭以及迁移能力。 方法 构建JUP稳定过表达或敲低的人HGSOC细胞株，在体外通过克隆形成、transwell细胞侵袭、划痕试验等观察JUP对HGSOC细胞增殖、侵袭、迁移的影响；建立裸鼠皮下成瘤模型，动态监测肿瘤生长、腹腔结节形成明确JUP对HGSOC肿瘤增殖及转移的影响；结合免疫共沉淀（Co-IP）实验筛选JUP发挥作用的下游分子；利用实时荧光定量PCR（RT-qPCR）、Western blot及组蛋白甲基转移酶活性试剂盒验证JUP对SETDB1表达及酶活性的影响；在JUP敲低后回补SETDB1，观察对HGSOC细胞恶性表型的挽救作用。 结果 JUP在HGSOC组织中显著高表达（P < 0.000 1），且高表达患者预后较差（P < 0.05）。体外实验表明，JUP过表达促进肿瘤细胞增殖、侵袭和迁移，而敲低JUP则抑制这些恶性表型（P < 0.01）。体内实验进一步证实JUP促进肿瘤生长和腹腔转移。机制研究发现，JUP与SETDB1直接结合并增强其甲基转移酶活性，敲低SETDB1可逆转JUP的促癌作用（P < 0.05）。 结论 JUP通过结合并调控SETDB1酶活性从而促进HGSOC的恶性进展，可能成为HGSOC潜在治疗靶点。

Objective To investigate the role of junction plakoglobin （JUP） in high-grade serous ovarian cancer （HGSOC） and its influence on SET domain bifurcated 1 （SETDB1）. Methods Human HGSOC cell lines with stable JUP overexpression or knockdown were established. The impact of JUP on cell proliferation， invasion， and migration was evaluated in vitro using colony formation， Transwell invasion， and wound healing assays. A subcutaneous xenograft model in nude mice was generated to dynamically monitor tumor growth and peritoneal nodule development， thereby elucidating the role of JUP in tumoral proliferation and metastasis. Co-immunoprecipitation （Co-IP） assays were performed to identify downstream molecules regulated by JUP. RT-qPCR， Western blotting， and histone methyltransferase activity assays were utilized to validate the influence of JUP on SETDB1 expression and enzymatic activity. Furthermore， rescue experiments were conducted to assess whether reconstitution of SETDB1 could reverse the malignant phenotypes induced by JUP knockdown in HGSOC cells. Results JUP was significantly overexpressed in high-grade serous ovarian cancer （HGSOC） tissues （P < 0.000 1）， and patients with elevated JUP expression exhibited a poorer prognosis （P < 0.05）. In vitro experiments demonstrated that JUP overexpression enhanced tumor cell proliferation， invasion， and migration， whereas JUP knockdown suppressed these malignant phenotypes （P < 0.01）. In vivo studies further confirmed that JUP promoted tumor growth and peritoneal metastasis. Mechanistic analyses revealed that JUP directly interacts with SETDB1 and enhances its methyltransferase activity； notably， the oncogenic effects induced by JUP overexpression were reversed upon SETDB1 knockdown （P < 0.05）. Conclusion JUP promotes the malignant progression of HGSOC by directly binding to and modulating the enzymatic activity of SETDB1， highlighting its potential as a therapeutic target for HGSOC.