Liu Rong, Lu Shumin, Deng Yan, Yang Shuyun, He Song, Cai Jing, Qiang Fulin, Chen Chen, Zhang Weiwei, Zhao Shuyang, Qian Li, Mao Guoxin, Wang Yingying
Department of Gynecologic Oncology, Nantong University Cancer Hospital, Nantong, 226001, Jiangsu Province, People's Republic of China.
Department of Oncology, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu Province, People's Republic of China.
Arch Gynecol Obstet. 2016 Jun;293(6):1297-307. doi: 10.1007/s00404-015-3904-x. Epub 2015 Oct 6.
In this study, we investigated the expression and role of PSMB4 in human epithelial ovarian cancer(EOC).
Western blot was used to evaluate the expression of PSMB4 in EOC tissues, and immunohistochemical analysis was performed on 115 cases of ovarian cancers. Then, we used Fisher exact test to analyze the correlation between PSMB4 and clinicopathological parameters. Starvation and re-feeding assay was used to assess cell cycle. CCK-8 assay and plate colony formation assay showed the influence of PSMB4 on proliferation of EOC cells.
The expression of PSMB4 in EOC tissues was higher than normal ovary tissues and was significantly associated with clinical pathologic variables. Kaplan-Meier curve showed that high expression of PSMB4 was related to poor prognosis of EOC patients. Starvation and re-feeding assay suggested that PSMB4 played a critical role in EOC cell proliferation. CCK-8 assay and plate colony formation assay showed that EOC cells treated with PSMB4-siRNA reduced cell proliferation of EOC cells. Additionally, PSMB4 knockdown decreased NF-κB activity. PSMB4 also regulated the expression of NF-κB mediated proteins, including cyclin D1, and cyclin E which involved in cell proliferation.
Our findings implied that PSMB4 is involved in the progression of EOC and could serve as potential therapeutical target of EOC. These data suggested that PSMB4 may promote cell proliferation via the NF-κB-target gene in EOC.
在本研究中,我们调查了蛋白酶体β型亚基4(PSMB4)在人上皮性卵巢癌(EOC)中的表达及作用。
采用蛋白质印迹法评估PSMB4在EOC组织中的表达,并对115例卵巢癌进行免疫组织化学分析。然后,我们使用Fisher精确检验分析PSMB4与临床病理参数之间的相关性。采用饥饿和再喂养试验评估细胞周期。CCK-8试验和平板集落形成试验显示PSMB4对EOC细胞增殖的影响。
PSMB4在EOC组织中的表达高于正常卵巢组织,且与临床病理变量显著相关。Kaplan-Meier曲线显示,PSMB4高表达与EOC患者预后不良有关。饥饿和再喂养试验表明,PSMB4在EOC细胞增殖中起关键作用。CCK-8试验和平板集落形成试验显示,用PSMB4-siRNA处理的EOC细胞降低了EOC细胞的增殖。此外,PSMB4基因敲低降低了核因子κB(NF-κB)活性。PSMB4还调节NF-κB介导的蛋白质的表达,包括参与细胞增殖的细胞周期蛋白D1和细胞周期蛋白E。
我们的研究结果表明,PSMB4参与了EOC的进展,可作为EOC的潜在治疗靶点。这些数据表明,PSMB4可能通过EOC中的NF-κB靶基因促进细胞增殖。