Zhang Yongquan, Sun Hong, He Guangxiang, Liu An, Wang Fengjun, Wang Lu
Department of Otorhinolaryngology Head and Neck Surgery, Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, China.
Tumour Biol. 2014 Aug;35(8):7651-7. doi: 10.1007/s13277-014-2034-6. Epub 2014 May 7.
Wild-type p53-induced phosphatase (WIP1) is overexpressed and functionally altered in multiple human malignancies. The present study investigated its abnormal expression and dysfunctions in nasopharyngeal carcinoma (NPC) in vitro. Here, analysis of WIP1 mRNA and protein in human NPC tissues revealed that both WIP1 messenger RNA (mRNA) and protein were elevated and were correlated with NPC clinical stage and metastasis in patients. In vitro experiments further showed that WIP1 inhibition led to a decrease in the proliferative ability of NPC CNE-2 and 5-8F cells accompanied by cell cycle arrest and increased apoptosis. In addition, WIP1 knockdown inhibited the invasiveness of CNE-2 and 5-8F cells and was associated with the down-regulation of the expression of matrix metallopeptidase 9 (MMP-9) mRNA and protein. Taken together, our data demonstrate that WIP1 regulates the proliferation and invasiveness of NPC cells in vitro, and this may be correlated with its modulation of MMP-9 expression, cell cycle progression and apoptosis. WIP1 functioned as a potential therapeutic target in NPC management.
野生型p53诱导的磷酸酶（WIP1）在多种人类恶性肿瘤中过表达且功能改变。本研究在体外研究了其在鼻咽癌（NPC）中的异常表达和功能障碍。在此，对人NPC组织中WIP1 mRNA和蛋白的分析显示，WIP1信使核糖核酸（mRNA）和蛋白均升高，且与患者的NPC临床分期和转移相关。体外实验进一步表明，WIP1抑制导致NPC CNE-2和5-8F细胞增殖能力下降，伴有细胞周期停滞和凋亡增加。此外，WIP1基因敲低抑制了CNE-2和5-8F细胞的侵袭性，并与基质金属肽酶9（MMP-9）mRNA和蛋白表达下调相关。综上所述，我们的数据表明，WIP1在体外调节NPC细胞的增殖和侵袭性，这可能与其对MMP-9表达、细胞周期进程和凋亡的调节有关。WIP1作为NPC治疗中的潜在靶点发挥作用。
