Lin Fei, Xie Zuopiao, Chang Li, Li Wenhui, Wang Li, Hou Yu, Li Lan, Zhu Junbo, Xia Yaoxiong, He Wenjie, Li Wenhui
Department of Radiation Oncology, The Third Affiliated Hospital of Kunming Medical University, Tumor Hospital of Yunnan Province Kunming, China.
Department of Emergency, The Second People's Hospital of Yunnan Province China.
Int J Clin Exp Pathol. 2017 Nov 1;10(11):11014-11021. eCollection 2017.
USP is one protease family of deubiquitylating enzyme (DUB). It removes ubiquitin from substrate and stabilizes the substrate. Here, we scanned several novel deubiquitinate enzymes in breast cancer tissue samples, and found that USP43 was up-regulated in breast cancer and closely relationship with metastasis, tumor size and a poor prognosis. Consequently, CCK-8 assay and colony formation assay were used to assess the function of USP43 in cell proliferation. Moreover, cell apoptosis assay and cell cycle assay revealed that USP43 facilitated cells G/S phase transition, but had slightly influence in cell apoptosis. EMT is a current event in breast cancer; the cells which happened have strong metastasis ability. We next detected whether USP43 regulated EMT, our results demonstrated that USP43 promoted EMT through regulated snail, thereby facilitated breast cancer cells metastasis. In brief, our works showed a novel mechanism of USP43 in facilitating breast cancer cells proliferation and metastasis. In addition, USP43 might be a novel therapeutic target for breast carcinoma.
泛素特异性蛋白酶(USP)是去泛素化酶(DUB)的一个蛋白酶家族。它从底物上去除泛素并使底物稳定。在此,我们在乳腺癌组织样本中筛选了几种新型去泛素化酶,发现USP43在乳腺癌中上调,且与转移、肿瘤大小及不良预后密切相关。因此,采用CCK - 8法和集落形成试验评估USP43在细胞增殖中的作用。此外,细胞凋亡试验和细胞周期试验表明,USP43促进细胞G/S期转换,但对细胞凋亡影响较小。上皮 - 间质转化(EMT)是乳腺癌中的一个常见事件;发生EMT的细胞具有很强的转移能力。接下来我们检测了USP43是否调节EMT,结果表明USP43通过调节蜗牛蛋白促进EMT,从而促进乳腺癌细胞转移。简而言之,我们的研究揭示了USP43促进乳腺癌细胞增殖和转移的新机制。此外,USP43可能是乳腺癌的一个新治疗靶点。