Prohibitin-2 Promotes Hepatocellular Carcinoma Malignancy Progression in Hypoxia Based on a Label-free Quantitative Proteomics Strategy
Prohibitin-2 Promotes Hepatocellular Carcinoma Malignancy Progression in Hypoxia Based on a Label-free Quantitative Proteomics Strategy
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DOI：
10.1002/mc.22040
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发表时间：
2014-10-01
影响因子：
4.6
通讯作者：
Zhou, Lin
中科院分区：
文献类型：
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作者：
Cheng, Jun;Gao, Feng;Zhou, Lin
肝细胞癌（HCC）的快速生长导致肿瘤缺氧是一种常见的病理现象。同时，肿瘤缺氧可促进肿瘤细胞生物学特性的改变。它可以增强肿瘤细胞在应激条件下的存活，导致对凋亡和血管生成的抵抗。能够调节HCC细胞恶性表型的分子在很大程度上仍是未知的。基于无标记的定量蛋白质组学数据，我们发现了一个显着的抑制素-2（PHB 2）在肝癌组织中的上调。用针对PHB 2的小干扰RNA处理肝癌细胞抑制细胞生长和集落形成，导致G1期停滞并使HCC细胞对凋亡敏感。此外，PHB 2表达的抑制显着抑制肝癌细胞适应缺氧微环境和抵抗化疗诱导的凋亡的能力。因此，肝癌中的PHB 2支持肝细胞恶性肿瘤向缺氧的发展和进展，并暗示PHB 2在经动脉化疗栓塞治疗中的潜在拮抗剂功能。(c)2013 Wiley Periodicals，Inc.
The rapid growth of hepatocellular carcinoma (HCC) leading to tumor hypoxia is a common pathological phenomenon. Meanwhile, tumor hypoxia can promote a change in the biological properties of tumor cells. It may enhance the survival of tumor cells under stress conditions, resulting in resistance to apoptosis and angiogenesis. The moleculars that could modulate the malignant phenotypes of HCC cells remain largely unknown. Based on label-free quantitative proteomic data, we found a significant upregulation of prohibitin-2 (PHB2) in HCC tissues. Treatment of hepatoma cells with small interfering RNAs against PHB2 suppressed cell growth and colony formation, led to G1 phase arrest and sensitized HCC cells to apoptosis. Moreover, inhibition of PHB2 expression dramatically repressed the ability of HCC cells to adapt to hypoxic microenvironments and resist chemotherapy-induced apoptosis. Thus, PHB2 in HCC supports the development and progression of hepatocellular malignancy to hypoxia, and implicates the potential antagonist function of PHB2 in transarterial chemoembolization treatment. (c) 2013 Wiley Periodicals, Inc.