More than 70% of patients with ovarian cancer are diagnosed in advanced stages. Therefore, it is urgent to identify a promising prognostic marker and understand the mechanism of ovarian cancer metastasis development. By using proteomics approaches, we found that UDP‐glucose dehydrogenase (UGDH) was up‐regulated in highly metastatic ovarian cancer TOV21G cells, characterized by high invasiveness (TOV21G^HI), in comparison to its parental control. Previous reports demonstrated that UGDH is involved in cell migration, but its specific role in cancer metastasis remains unclear. By performing immunohistochemical staining with tissue microarray, we found overexpression of UGDH in ovarian cancer tissue, but not in normal adjacent tissue. Silencing using RNA interference (RNAi) was utilized to knockdown UGDH, which resulted in a significant decrease in metastatic ability in transwell migration, transwell invasion and wound healing assays. The knockdown of UGDH caused cell cycle arrest in the G₀/G₁ phase and induced a massive decrease of tumour formation rate in vivo. Our data showed that UGDH‐depletion led to the down‐regulation of epithelial‐mesenchymal transition (EMT)‐related markers as well as MMP2, and inactivation of the ERK/MAPK pathway. In conclusion, we found that the up‐regulation of UGDH is related to ovarian cancer metastasis and the deficiency of UGDH leads to the decrease of cell migration, cell invasion, wound healing and cell proliferation ability. Our findings reveal that UGDH can serve as a prognostic marker and that the inhibition of UGDH is a promising strategy for ovarian cancer treatment.

中文翻译：

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靶向UDP-葡萄糖脱氢酶可抑制卵巢癌的生长和转移。

超过70％的卵巢癌患者被诊断为晚期。因此，迫切需要确定有希望的预后标志物，并了解卵巢癌转移发展的机制。通过使用蛋白质组学方法，我们发现UDP-葡萄糖脱氢酶（UGDH）在高度转移性卵巢癌TOV21G细胞中被上调，其特征是高侵袭性（TOV21G ^HI），与其家长控制相比。先前的报道表明UGDH参与细胞迁移，但其在癌症转移中的具体作用仍不清楚。通过用组织微阵列进行免疫组织化学染色，我们发现卵巢癌组织中UGDH的过度表达，而正常邻近组织中没有。利用RNA干扰（RNAi）沉默来敲低UGDH，这大大降低了Transwell迁移，Transwell入侵和伤口愈合实验中的转移能力。UGDH的敲低导致细胞周期停滞在G ₀ / G ₁并诱导体内肿瘤形成率大幅降低。我们的数据显示，UGDH耗竭导致上皮-间质转化（EMT）相关标记以及MMP2的下调，并导致ERK / MAPK通路失活。总之，我们发现UGDH的上调与卵巢癌转移有关，UGDH的缺乏导致细胞迁移，细胞侵袭，伤口愈合和细胞增殖能力降低。我们的发现表明，UGDH可以作为预后指标，而UGDH的抑制是卵巢癌治疗的有希望的策略。