Rab31 promoted hepatocellular carcinoma (HCC) progression via inhibition of cell apoptosis induced by PI3K/AKT/Bcl-2/BAX pathway
Rab31 promoted hepatocellular carcinoma (HCC) progression via inhibition of cell apoptosis induced by PI3K/AKT/Bcl-2/BAX pathway
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DOI：
10.1007/s13277-015-3626-5
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发表时间：
2015-11-01
期刊：
影响因子：
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通讯作者：
Zhao, Dongli
中科院分区：
文献类型：
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作者：
Sui, Yanxia;Zheng, Xiaoqiang;Zhao, Dongli
Rab 31属于小GTP结合蛋白Ras超家族，已发现其调节囊泡从高尔基体到早期和晚期内体的运输。本研究检测96例肝细胞癌（HCC）组织中Rab 31的表达，探讨Rab 31表达与HCC术后预后的关系。免疫组织化学染色发现Rab 31在肝癌组织中的表达明显高于癌旁肝组织。肝癌组织中Rab 31的异常过表达与肝切除术后预后不良相关。单因素分析显示，晚期肝癌TNM分期、肝内转移、门静脉侵犯、Rab 31增高是预后不良的预测因素。多因素分析显示，肝内转移和Rab 31增高是独立的预后因素。此外，Rab 31在Huh 7细胞中的强制表达被发现通过上调PI 3 K/AKT诱导的Bcl-2/BAX比率来促进细胞生长。相应地，沉默Rab 31诱导细胞凋亡，进而抑制体外MHCC 97细胞的生长能力。综上所述，本研究提供了Rab 31在HCC中过表达的证据，Rab 31可能用作HCC患者预后不良的新生物标志物。PI 3 K/AKT/Bcl-2/BAX轴参与Rab 31促进HCC进展。
Rab31 belongs to the Ras superfamily of small GTP-binding proteins, which has been found to regulate the vesicle transport from the Golgi apparatus to early and late endosomes. The investigation here detected the expression of Rab31 in 96 patients with hepatocellular carcinoma (HCC) and tried to identify its significance on outcome of HCCs after liver resection. By immunohistochemistry staining, it was found that Rab31 expression in HCC tissues was remarkably higher than that in adjacent liver tissues. Aberrant Rab31 overexpression in HCC tissues was identified to be associated with worse prognosis after liver resection. Univariate analysis showed that advanced tumor-nodes-metastasis (TNM) staging of HCC, intrahepatic metastases, portal vein invasion, and higher Rab31 were the predictive factors of poor prognosis. Multivariate analysis demonstrated that intrahepatic metastases and higher Rab31 were the independent prognostic factors. Furthermore, forced expression of Rab31 in Huh7 cells was found to promote cell growth via upregulation of Bcl-2/BAX ratio induced by PI3K/AKT. Correspondingly, silencing Rab31 induced cell apoptosis and in turn suppressed the growth capacity of MHCC97 cells in vitro. Taken together, this study provides the evidence of Rab31 overexpression in HCC, and Rab31 is potentially used as a novel biomarker of poor prognosis in patients with HCC. PI3K/AKT/Bcl-2/BAX axis was involved in Rab31-promoting HCC progression.