Li Pengyu, Zhang Lili, Yang Muyi, Qi Mei, Jin Xing, Han Bo
Department of Emergency Surgery, Shandong University Qilu Hospital, Jinan, Shandong 250012, P.R. China.
Department of Pathology, Shandong University Medical School, Jinan, Shandong 250012, P.R. China.
Oncol Lett. 2017 Aug;14(2):1265-1274. doi: 10.3892/ol.2017.6297. Epub 2017 Jun 1.
Cullin 4B (Cul4B), a scaffold protein that assembles the ubiquitin ligase complex, is involved in a wide variety of physiological and developmental processes, such as cell cycle progression, DNA damage response and gene expression regulation. Cul4B is overexpressed in various solid tumors. However, the prognostic value and role of Cul4B in cholangiocarcinoma (CCA) is largely unknown. The present study demonstrated that Cul4B was overexpressed in 21 (26.6%) of 79 patients with intrahepatic CCA, and in 40 (28.6%) of 140 patients with extrahepatic CCA (EHCC). Kaplan-Meier survival analysis suggested that Cul4B expression is an unfavorable prognostic factor in EHCC patients. Notably, Cul4B and epidermal growth factor receptor expression define a subset of CCA patients with poor prognosis. data indicated that Cul4B promotes the proliferation, migration and invasion of CCA cells. Furthermore, Cul4B expression promotes the epithelial-mesenchymal transition (EMT) process in CCA cells. Finally, Cul4B repressed the expression of the tumor suppressor genes P16 and phosphatase and tensin homolog. Collectively, the results of the present study revealed an important role of Cul4B in CCA with respect to initiating EMT. Cul4B expression may serve as a prognostic marker for patients with EHCC.
Cullin 4B(Cul4B)是一种组装泛素连接酶复合物的支架蛋白,参与多种生理和发育过程,如细胞周期进程、DNA损伤反应和基因表达调控。Cul4B在各种实体瘤中均有过表达。然而,Cul4B在胆管癌(CCA)中的预后价值和作用在很大程度上尚不清楚。本研究表明,在79例肝内CCA患者中,21例(26.6%)Cul4B过表达;在140例肝外CCA(EHCC)患者中,40例(28.6%)Cul4B过表达。Kaplan-Meier生存分析表明,Cul4B表达是EHCC患者预后不良的一个因素。值得注意的是,Cul4B和表皮生长因子受体表达共同确定了一部分预后不良的CCA患者。数据表明,Cul4B可促进CCA细胞的增殖、迁移和侵袭。此外,Cul4B表达可促进CCA细胞的上皮-间质转化(EMT)过程。最后,Cul4B可抑制肿瘤抑制基因P16和磷酸酶及张力蛋白同源物的表达。总的来说,本研究结果揭示了Cul4B在CCA启动EMT过程中的重要作用。Cul4B表达可能作为EHCC患者的一个预后标志物。