High expression of vacuolar protein sorting 4B (VPS4B) is associated with accelerated cell proliferation and poor prognosis in human hepatocellular carcinoma
High expression of vacuolar protein sorting 4B (VPS4B) is associated with accelerated cell proliferation and poor prognosis in human hepatocellular carcinoma
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液泡蛋白分选 4B (VPS4B) 的高表达与人肝细胞癌细胞增殖加速和不良预后相关
DOI：
10.1016/j.prp.2014.11.013
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发表时间：
2015-01-01
影响因子：
2.8
通讯作者：
Lu, Cuihua
中科院分区：
文献类型：
--
作者：
Jiang, Dawei;Hu, Baoying;Lu, Cuihua
极性蛋白分选4 B（VPS 4 B）是ATP酶家族的一员，在病毒的形成、出芽和胞质分裂等过程中发挥重要作用。在这项研究中，我们研究了VPS 4 B在人肝细胞癌（HCC）中的预后作用及其对HCC细胞生长的影响。Western blot和免疫组化分析显示，VPS 4 B在98例HCC组织中显著上调，与邻近的非肿瘤样品相比。同时，临床病理变量和单因素及多因素生存分析显示，VPS 4 B高表达与多个临床病理因素相关，包括AJCC分期、微血管浸润、Ki-67和预后不良。更重要的是，单变量和多变量生存分析表明，VPS 4 B作为HCC患者生存的独立预后因素。此外，我们发现VPS 4 B在血清饥饿的Huh 7和HepG 2 HCC细胞中低表达，并且在血清再喂养后进行性增加。为了研究VPS 4 B是否能够调控肝癌细胞的增殖，我们通过转染VPS 4 B-siRNA寡核苷酸，在Huh 7和HepG 2细胞中敲低VPS 4 B。流式细胞术和CCK-8检测结果表明，VPS 4 B的干扰导致细胞周期阻滞和细胞增殖减少。综上所述，我们的研究结果表明，VPS 4 B可能是一个候选的预后生物标志物，以及一个潜在的治疗肝癌的目标。(C)2014 Elsevier GmbH. All rights reserved.
Vacuolar protein sorting 4B (VPS4B) is a member of ATPase family proteins that have been shown to play important roles in the formation of MVBs, virus budding and abscission of cytokinesis. In this study, we investigated the prognostic role of VPS4B in human hepatocellular carcinoma (HCC) and its effect on the growth of HCC cells. Western blot and immunohistochemistrical analyses revealed that VPS4B was significantly upregulated in 98 HCC tissues, compared with adjacent nontumorous samples. Meanwhile, clinicopathological variables and univariate and multivariate survival analyses showed that high VPS4B expression was correlated with multiple clinicopathological factors, including AJCC stage, microvascular invasion, Ki-67 and a poor prognosis. More importantly, univariate and multivariate survival analyses demonstrated that VPS4B served as an independent prognostic factor for survival in HCC patients. Furthermore, we found that VPS4B was lowly expressed in serum-starved Huh7 and HepG2 HCC cells, and was progressively increased after serum-refeeding. To study whether VPS4B could regulate the proliferation of HCC cells, VPS4B was knocked down in both Huh7 and HepG2 cells through the transfection of VPS4B-siRNA oligos. Flow cytometry and CCK-8 assay results indicated that interference of VPS4B led to cell cycle arrest and reduced cell proliferation of HCC cells. Taken together, our results implied that VPS4B could be a candidate prognostic biomarker as well as a potential therapeutical target of HCC. (C) 2014 Elsevier GmbH. All rights reserved.