High CHMP4B expression is associated with accelerated cell proliferation and resistance to doxorubicin in hepatocellular carcinoma
High CHMP4B expression is associated with accelerated cell proliferation and resistance to doxorubicin in hepatocellular carcinoma
复制标题
CHMP4B 高表达与肝细胞癌中细胞增殖加速和阿霉素耐药相关
DOI：
10.1007/s13277-014-2873-1
复制
发表时间：
2015-04-01
期刊：
影响因子：
--
通讯作者：
Wan, Chunhua
中科院分区：
文献类型：
--
作者：
Hu, Baoying;Jiang, Dawei;Wan, Chunhua
荷电多泡体蛋白4 B（Charged multiple-esicular body protein 4 B，CHMP 4 B）是内体分选复合物（ESCRT）-Ⅲ复合物的一个亚基，在细胞动力学膜破裂和有丝分裂后期起重要作用。在这项研究中，我们探讨了CHMP 4 B在人肝细胞癌（HCC）中的预后意义及其对HCC细胞生理学的影响。Western blot和免疫组化分析显示，CHMP 4 B在HCC组织中的表达明显高于癌旁组织。同时，临床病理分析显示CHMP 4 B高表达与AFP、肝硬化、AJCC分期、Ki-67表达及预后不良等多个临床病理变量相关。更重要的是，单因素和多因素生存分析表明，CHMP 4 B作为一个独立的预后因素的生存肝癌患者。使用HCC细胞培养物，我们发现CHMP 4 B的表达在从血清饥饿释放后进行性上调。为了验证CHMP 4 B是否可以调节肝癌细胞的增殖，通过转染CHMP 4 B-siRNA oligos来敲低CHMP 4 B。流式细胞术和CCK-8检测表明，CHMP 4 B的干扰导致细胞周期阻滞和肝癌细胞的增殖障碍。此外，CHMP 4 B表达的耗竭可增加HepG 2和Huh 7细胞对阿霉素的敏感性。总而言之，我们的结果表明CHMP 4 B可能是一种有前途的预后生物标志物，也是肝癌的潜在治疗靶点。
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.