Cheng Jialin, Su Min, Jin Yunfeng, Xi Qinghua, Deng Yan, Chen Jie, Wang Wei, Chen Yannan, Chen Lingling, Shi Nannan, Mao Guoxin
1 Department of Oncology, Affiliated Hospital of Nantong University, Nantong University, Nantong, People's Republic of China.
2 Department of Obstetrics and Gynecology, Affiliated Hospital of Nantong University, Nantong University, Nantong, People's Republic of China.
Tumour Biol. 2017 Mar;39(3):1010428317694543. doi: 10.1177/1010428317694543.
As a crucial member of the small ubiquitin-like modifier system, SUMO-specific protease 3, was identified to be essential for cell proliferation and ribosomal RNA processing. Recent studies showed that SUMO-specific protease 3 was elevated in ovarian cancer compared to normal tissue samples. However, the connection between SUMO-specific protease 3-specific expression and clinicopathological parameters of epithelial ovarian cancer, as well as the physiologically potential role of SUMO-specific protease 3 in epithelial ovarian cancer remained unclear. In this study, an analysis of 124 paraffin-embedded slices by immunohistochemistry indicated that SUMO-specific protease 3 expression was positively correlated with the International Federation of Gynecology and Obstetrics stages (p = 0.025), tumor grade (p = 0.004), and lymph node metastasis (p = 0.001) and was also a critical prognostic factor for the overall survival of epithelial ovarian cancer patients, as revealed by Kaplan-Meier curve analysis. Knockdown of SUMO-specific protease 3 weakened the proliferation, migration, and invasion capability of ovarian cancer cells, down-regulated the expression of Proliferating Cell Nuclear Antigen, Forkhead Box C2, and N-cadherin, and resulted in upregulation of p21 and E-cadherin. Consistent with our results, SUMO-specific protease 3 had been verified to promote cell proliferation, metastasis, and tumorigenesis in multiple malignant cancers, which was a redox-sensitive molecule mediating the epithelial-mesenchymal transition. Collectively, our findings for the first time specifically supported that SUMO-specific protease 3 might play an important role in the regulation of epithelial ovarian cancer progression and could serve as a potential biomarker for prognosis as well as provide a promising therapeutic target against epithelial ovarian cancer.
作为小泛素样修饰物系统的关键成员，SUMO特异性蛋白酶3被确定对细胞增殖和核糖体RNA加工至关重要。最近的研究表明，与正常组织样本相比，SUMO特异性蛋白酶3在卵巢癌中表达升高。然而，SUMO特异性蛋白酶3的特异性表达与上皮性卵巢癌临床病理参数之间的联系，以及SUMO特异性蛋白酶3在上皮性卵巢癌中的生理潜在作用仍不清楚。在本研究中，通过免疫组织化学对124例石蜡包埋切片进行分析表明，SUMO特异性蛋白酶3的表达与国际妇产科联盟分期（p = 0.025）、肿瘤分级（p = 0.004）和淋巴结转移（p = 0.001）呈正相关，并且也是上皮性卵巢癌患者总生存的关键预后因素，这由Kaplan-Meier曲线分析揭示。敲低SUMO特异性蛋白酶3会削弱卵巢癌细胞的增殖、迁移和侵袭能力，下调增殖细胞核抗原、叉头框C2和N-钙黏蛋白的表达，并导致p21和E-钙黏蛋白上调。与我们的结果一致，SUMO特异性蛋白酶3已被证实可促进多种恶性肿瘤中的细胞增殖、转移和肿瘤发生，它是介导上皮-间质转化的氧化还原敏感分子。总的来说，我们的研究结果首次明确支持SUMO特异性蛋白酶3可能在上皮性卵巢癌进展的调控中发挥重要作用，并可作为潜在的预后生物标志物，还为上皮性卵巢癌提供了有前景的治疗靶点。
