Liang Bo, Zheng Wenjuan, Fang Lu, Wu Linquan, Zhou Fan, Yin Xiangbao, Yu Xin, Zou Zhenhong
a Department of General Surgery , The Second Affiliated Hospital of Nanchang University , Nanchang , Jiangxi , China.
b Jiangxi Provincial Center for Disease Control and Prevention , Nanchang , Jiangxi , China.
Cancer Biol Ther. 2016 Aug 2;17(8):824-32. doi: 10.1080/15384047.2016.1195046. Epub 2016 Jun 17.
The targeting protein for Xenopus kinesin-like protein 2 (TPX2) is a putative oncogene in different human cancers. This study assessed TPX2 expression in gastric cancer tissue samples and then determined the effects of TPX2 knockdown on the regulation of gastric cancer cell malignant behaviors in vitro. Tissue samples from 115 gastric cancer patients were analyzed for TPX2 expression. The effects of TPX2 siRNA on gastric cancer cells were assessed in vitro, including cell viability, cell cycle distribution, apoptosis, migration, and invasion. The data showed that TPX2 was overexpressed in gastric cancer tissues compared to that in the adjacent normal epithelia. Moreover, TPX2 overexpression was associated with a poor overall survival and was an independent prognostic predictor of gastric cancer. In addition, the in vitro study further confirmed the ex vivo data, i.e., knockdown of TPX2 expression reduced gastric cancer cell viability but induced apoptosis and arrested cells at the G2/M phase of the cell cycle. Knockdown of TPX2 expression also inhibited the tumor cell migration and invasion capacity in vitro. At the gene level, knockdown of TPX2 expression upregulated the levels of cyclin B1, cdk4, p53, Bax, caspase-3, and E-cadherin, but downregulated the levels of cyclin D1, cdk2, N-cadherin, slug, matrix metalloprotease (MMP)-2, and MMP-9, suggesting that knockdown of TPX2 expression suppressed tumor cell epithelial-mesenchymal transition (EMT). This study demonstrated that detection of TPX2 overexpression could serve as a prognostic marker and therapeutic target for gastric cancer.
非洲爪蟾驱动蛋白样蛋白2(TPX2)的靶向蛋白是不同人类癌症中的一种假定癌基因。本研究评估了TPX2在胃癌组织样本中的表达,然后确定了TPX2基因敲低对体外胃癌细胞恶性行为调控的影响。分析了115例胃癌患者组织样本中的TPX2表达情况。在体外评估了TPX2 siRNA对胃癌细胞的影响,包括细胞活力、细胞周期分布、凋亡、迁移和侵袭。数据显示,与相邻正常上皮组织相比,TPX2在胃癌组织中过表达。此外,TPX2过表达与总体生存率低相关,是胃癌的独立预后预测指标。此外,体外研究进一步证实了体外实验数据,即TPX2表达的敲低降低了胃癌细胞活力,但诱导了凋亡并使细胞停滞在细胞周期的G2/M期。TPX2表达的敲低在体外也抑制了肿瘤细胞的迁移和侵袭能力。在基因水平上,TPX2表达的敲低上调了细胞周期蛋白B1、细胞周期蛋白依赖性激酶4(cdk4)、p53、Bax、半胱天冬酶-3和E-钙黏蛋白的水平,但下调了细胞周期蛋白D1、cdk2、N-钙黏蛋白、蜗牛蛋白、基质金属蛋白酶(MMP)-2和MMP-9的水平,表明TPX2表达的敲低抑制了肿瘤细胞上皮-间质转化(EMT)。本研究表明,检测TPX2过表达可作为胃癌的预后标志物和治疗靶点。