Jumonji domain-containing 6 (JMJD6) is a candidate gene associated with tumorigenesis, and JMJD6 overexpression predicts poor differentiation and unfavorable survival in some cancers. However, there are no studies reporting the expression of JMJD6 in ovarian cancer, and no JMJD6 inhibitors have been developed and applied to targeted cancer therapy research. In the present study, we found that the high expression of JMJD6 in ovarian cancer was correlated with poor prognosis in ovarian cancer. A potential inhibitor (SKLB325) was designed based on the crystal structure of the jmjC domain of JMJD6. This molecule significantly suppressed proliferation and induced apoptosis in a dose-dependent manner in SKOV3 cell lines as detected by CCK-8 cell proliferation assays and flow cytometry. A Matrigel endothelial tube formation assay showed that SKLB325 inhibited capillary tube organization and migration in HUVECs in vitro. We also observed that JMJD6 colocalized with p53 protein in the nucleus, with mRNA and protein expression of p53 as well as its downstream effectors significantly increasing both in vitro and in intraperitoneal tumor tissues treated with SKLB325. In addition, SKLB325 significantly reduced the intraperitoneal tumor weight and markedly prolonged the survival of tumor-bearing mice. Taken together, our findings suggest that JMJD6 may be a marker of poor prognosis in ovarian cancer and that SKLB325 may be a potential candidate drug for the treatment of ovarian cancer.

Jumonji 结构域包含 6 (JMJD6) 是与肿瘤发生相关的候选基因，JMJD6 过表达预示着某些癌症的分化不良和不利的生存。然而，目前还没有研究报道JMJD6在卵巢癌中的表达，也没有JMJD6抑制剂被开发出来并应用于癌症靶向治疗研究。在本研究中，我们发现卵巢癌中JMJD6的高表达与卵巢癌的不良预后相关。根据JMJD6的jmjC结构域的晶体结构设计了一种潜在的抑制剂（SKLB325）。通过 CCK-8 细胞增殖测定和流式细胞术检测到，该分子在 SKOV3 细胞系中以剂量依赖性方式显着抑制增殖并诱导细胞凋亡。基质胶内皮管形成测定表明，SKLB325 抑制体外 HUVEC 的毛细管组织和迁移。我们还观察到 JMJD6 与 p53 蛋白共定位于细胞核中，p53 及其下游效应子的 mRNA 和蛋白表达在体外和经 SKLB325 处理的腹膜内肿瘤组织中均显着增加。此外，SKLB325显着降低腹膜内肿瘤重量并显着延长荷瘤小鼠的生存期。综上所述，我们的研究结果表明，JMJD6 可能是卵巢癌预后不良的标志物，而 SKLB325 可能是治疗卵巢癌的潜在候选药物。