Yang Xiaolin, Liu Geling, Xiao Hongzhen, Yu Fang, Xiang Xiuxiu, Lu Yifang, Li Weijuan, Liu Xiuling, Li Sha, Shi Yanping
Department of Endocrinology (Section I), Tangshan Workers Hospital, Tangshan, China.
Pathol Oncol Res. 2014 Jul;20(3):641-8. doi: 10.1007/s12253-014-9743-4. Epub 2014 Feb 1.
TPX2 (targeting protein for xenopus kinesin-like protein 2), a microtubule-associated protein, plays an important role in the formation of the mitotic spindle. Abnormal expression of TPX2 in various types of malignant tumors has been reported, but less is known for medullary thyroid cancer (MTC). We investigated the expression of TPX2 in human MTC tissues and its potential use as a therapeutic target. Immunohistochemical analysis of TPX2 expression was performed for 32 cases of MTC and 8 cases of normal thyroid. TPX2 expression was found to be significantly higher in MTC compared to normal thyroid tissues (P < 0.05), and to be associated with tumor size, lymph node metastasis, and advanced disease stage. The cellular effects of TPX2 knockdown, including cell proliferation, apoptosis, cell cycle diffusions, and mitotic gene expression were investigated using small interfering RNA (siRNA). TPX2-siRNA caused G1 and G2-phase cell cycle arrest, inhibited cell proliferation, and induced apoptosis. TPX2-siRNA also downregulated Aurora-A and cyclinB1 protein expression in MTC cells and enhanced the expression of p53 protein (P < 0.05). These results suggest that TPX2 may be of potential use as a new marker for MTC prognosis and therapy.
TPX2（非洲爪蟾驱动蛋白样蛋白2的靶向蛋白）是一种微管相关蛋白，在有丝分裂纺锤体的形成中起重要作用。已有报道称TPX2在各类恶性肿瘤中表达异常，但甲状腺髓样癌（MTC）方面的相关研究较少。我们研究了TPX2在人MTC组织中的表达及其作为治疗靶点的潜在用途。对32例MTC和8例正常甲状腺组织进行了TPX2表达的免疫组织化学分析。结果发现，与正常甲状腺组织相比，MTC中TPX2的表达显著更高（P < 0.05），且与肿瘤大小、淋巴结转移及疾病晚期相关。使用小干扰RNA（siRNA）研究了TPX2敲低对细胞的影响，包括细胞增殖、凋亡、细胞周期扩散及有丝分裂基因表达。TPX2-siRNA导致G1期和G2期细胞周期阻滞，抑制细胞增殖并诱导凋亡。TPX2-siRNA还下调了MTC细胞中Aurora-A和细胞周期蛋白B1的蛋白表达，并增强了p53蛋白的表达（P < 0.05）。这些结果表明，TPX2可能作为MTC预后和治疗的新标志物具有潜在用途。
