Hu Baoying, Jiang Dawei, Chen Yuyan, Wei Lixian, Zhang Shusen, Zhao Fengbo, Ni Runzhou, Lu Cuihua, Wan Chunhua
Basic Medical Research Centre, Medical College, Nantong University, Nantong, 226001, China.
Tumour Biol. 2015 Apr;36(4):2569-81. doi: 10.1007/s13277-014-2873-1. Epub 2015 Feb 11.
Charged multivesicular body protein 4B (CHMP4B), a subunit of the endosomal sorting complex required for transport (ESCRT)-III complex, plays an important part in cytokinetic membrane abscission and the late stage of mitotic cell division. In this study, we explored the prognostic significance of CHMP4B in human hepatocellular carcinoma (HCC) and its impact on the physiology of HCC cells. Western blot and immunohistochemistrical analyses showed that CHMP4B was significantly upregulated in HCC tissues, compared with adjacent non-tumorous tissues. Meanwhile, clinicopathological analysis revealed that high CHMP4B expression was correlated with multiple clinicopathological variables, including AFP, cirrhosis, AJCC stage, Ki-67 expression, and poor prognosis. More importantly, univariate and multivariate survival analyses demonstrated that CHMP4B served as an independent prognostic factor for survival of HCC patients. Using HCC cell cultures, we found that the expression of CHMP4B was progressively upregulated after the release from serum starvation. To verify whether CHMP4B could regulate the proliferation of HCC cells, CHMP4B was knocked down through the transfection of CHMP4B-siRNA oligos. Flow cytometry and CCK-8 assays indicated that interference of CHMP4B led to cell cycle arrest and proliferative impairment of HCC cells. Additionally, depletion of CHMP4B expression could increase the sensitivity to doxorubicin in HepG2 and Huh7 cells. Taken together, our results implied that CHMP4B could be a promising prognostic biomarker as well as a potential therapeutic target of HCC.
电荷多泡体蛋白4B（CHMP4B）是转运所需内体分选复合体（ESCRT）-III复合体的一个亚基，在细胞分裂的胞质分裂膜脱离和有丝分裂细胞分裂后期发挥重要作用。在本研究中，我们探讨了CHMP4B在人类肝细胞癌（HCC）中的预后意义及其对HCC细胞生理学的影响。蛋白质免疫印迹和免疫组织化学分析表明，与相邻的非肿瘤组织相比，CHMP4B在HCC组织中显著上调。同时，临床病理分析显示，CHMP4B高表达与多个临床病理变量相关，包括甲胎蛋白、肝硬化、美国癌症联合委员会（AJCC）分期、Ki-67表达及预后不良。更重要的是，单因素和多因素生存分析表明，CHMP4B是HCC患者生存的独立预后因素。利用HCC细胞培养，我们发现血清饥饿解除后CHMP4B的表达逐渐上调。为了验证CHMP4B是否能调节HCC细胞的增殖，通过转染CHMP4B-siRNA寡核苷酸敲低CHMP4B。流式细胞术和CCK-8检测表明，干扰CHMP4B会导致HCC细胞的细胞周期停滞和增殖受损。此外，CHMP4B表达的缺失可增加HepG2和Huh7细胞对阿霉素的敏感性。综上所述，我们的结果表明，CHMP4B可能是一种有前景的预后生物标志物以及HCC的潜在治疗靶点。
