TPX2 level correlates with cholangiocarcinoma cell proliferation, apoptosis, and EMT
TPX2 level correlates with cholangiocarcinoma cell proliferation, apoptosis, and EMT
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TPX2 水平与胆管癌细胞增殖、凋亡和 EMT 相关
DOI：
10.1016/j.biopha.2018.08.011
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发表时间：
2018
影响因子：
7.5
通讯作者：
Liang Bo
中科院分区：
文献类型：
--
作者：
Zou Zhenhong;Zheng Bingbing;Li Jiaxi;Lv Xiaorui;Zhang Han;Yu Fanqi;Kong Lingdong;Li Yimin;Yu Mengqi;Fang Lu;Liang Bo
目的胆管癌的分子特征尚不明确。非洲爪蟾驱动蛋白样蛋白2（TPX 2）的靶向蛋白已被证明在几种癌症的背景下促进肿瘤发生;然而，其在胆管癌中的作用尚未研究。方法采用免疫组织化学方法检测TPX 2在胆管癌中的表达水平。通过卡方检验评估潜在相关性。分别采用CCK-8法、流式细胞术和transwell法检测TPX 2表达对细胞增殖、细胞周期、凋亡、侵袭和迁移的影响。结果TPX 2在胆管癌组织中的表达明显高于癌旁组织（44.3%vs.5.7%，P<0.01）; TPX 2的过表达与肿瘤的TNM分期、淋巴结转移及预后呈正相关。下调TPX 2表达可诱导胆管癌细胞G2-M期阻滞、凋亡及侵袭和迁移能力的抑制。TPX 2 siRNA处理胆管癌细胞后，cyclin A1、cyclin B1、p53、Bax和E-cadherin表达上调，cyclin D1、CDK 2、Bcl-2、N-cadherin、β-cadherin、MMP-2、MMP-9、Slug和Twist 1表达下调。
PurposeThe molecular signatures of cholangiocarcinoma are not well characterized. Targeting protein for Xenopus kinesin-like protein 2 (TPX2) has been shown to promote oncogenesis in the context of several cancers; however, its’ role in cholangiocarcinoma has not been studied. We evaluated the role of TPX2 in cholangiocarcinoma.MethodsExpression levels of TPX2 in cholangiocarcinoma were assessed by immunohistochemistry. Potential correlations were assessed by Chi-squared test. Impact of TPX2 expression on cell proliferation, cell cycle, apoptosis, cell invasion and migration was investigated by CCK-8, flow cytometric analysis, and transwell assay, respectively. The expressions of cell-cycle, cell-apoptosis and EMT related target proteins were detected by immunoblotting.ResultsTPX2 expression in cholangiocarcinoma tissues was significantly higher than that paracancerous tissue (44.3%vs.5.7%;P<0.01). Overexpression of TPX2 showed a positive correlation with TNM stage, lymph node metastasis, and prognosis of patients. Knockdown of TPX2 expression induced G2-M arrest, apoptosis and inhibited invasion and migration of cholangiocarcinoma cells. Treatment of cholangiocarcinoma cells with TPX2 siRNA resulted in upregulation of cyclin A1, cyclin B1, p53, Bax, and E-cadherin; while downregulation of cyclin D1, CDK2, Bcl-2, N-cadherin, β-cadherin MMP-2, MMP-9, Slug, and Twist1.ConclusionsCollectively, these results indicate that TPX2 may serve as a potential biomarker of prognostic relevance and a potential therapeutic target for cholangiocarcinoma.