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高YBX1表达提示鼻咽癌预后不良,并促进其细胞迁移和侵袭。

High YBX1 expression indicates poor prognosis and promotes cell migration and invasion in nasopharyngeal carcinoma.

作者信息

Zhou Lei-Lei, Ni Jie, Feng Wan-Ting, Yao Rong, Yue Shun, Zhu Ya-Ning, Tang Hai-Yan, Lv Ling-Yun, Feng Ji-Feng, Zhu Wei-Guo

机构信息

Department of Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu, China.

Nanjing Medical University Affliated Cancer Hospital, Department of Clinical Cancer Research Center, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing, Jiangsu, China.

出版信息

Exp Cell Res. 2017 Dec 1;361(1):126-134. doi: 10.1016/j.yexcr.2017.10.009. Epub 2017 Oct 9.

DOI:10.1016/j.yexcr.2017.10.009
PMID:29024700
Abstract

Y-box binding protein-1 (YBX1) is a multifunctional protein and often acts as an indicator of poor prognosis in cancers. Increasing evidence has shown that the levels of YBX1 protein were closely associated with multidrug resistance, relapse, metastasis and poor prognosis in cancers. However, its role in nasopharyngeal carcinoma (NPC) metastasis remains unknown. In our study, we discovered that the expression of YBX1 was increased in nasopharyngeal carcinoma tissues. YBX1 protein levels positively correlated with T stage and metastasis of NPC patients. Moreover, expression of YBX1 was negatively correlated with membrane E-cadherin levels and positively correlated with Vimentin expression. In vitro, the expression of YBX1 was closely related to the invasive and migratory ability of nasopharyngeal carcinoma cells. Knockdown of YBX1 inhibited migration and invasion in 5-8F cells, and over-expression of YBX1 promoted CNE1 cells migration and invasion. Transforming growth factor-β1 (TGF-β1) treatment led to epithelial-to-mesenchymal transition (EMT) in CNE1 cells accompanied by elevated YBX1 expression. On the contrary, knockdown of YBX1 partially inhibited the TGF-β1-induced CNE1 cell migration, together with changes of EMT-associated markers. Our study revealed that TGF-β1/YBX1 signaling might be one of novel mechanisms mediating EMT in NPC, providing a new target for the treatment of nasopharyngeal carcinoma.

摘要

Y盒结合蛋白1(YBX1)是一种多功能蛋白,常作为癌症预后不良的指标。越来越多的证据表明,YBX1蛋白水平与癌症的多药耐药性、复发、转移及预后不良密切相关。然而,其在鼻咽癌(NPC)转移中的作用尚不清楚。在我们的研究中,我们发现鼻咽癌组织中YBX1的表达增加。YBX1蛋白水平与NPC患者的T分期和转移呈正相关。此外,YBX1的表达与膜E-钙黏蛋白水平呈负相关,与波形蛋白表达呈正相关。在体外,YBX1的表达与鼻咽癌细胞的侵袭和迁移能力密切相关。敲低YBX1可抑制5-8F细胞的迁移和侵袭,而YBX1的过表达则促进CNE1细胞的迁移和侵袭。转化生长因子-β1(TGF-β1)处理导致CNE1细胞发生上皮-间质转化(EMT),同时YBX1表达升高。相反,敲低YBX1可部分抑制TGF-β1诱导的CNE1细胞迁移,并伴随EMT相关标志物的变化。我们的研究表明,TGF-β1/YBX1信号可能是介导NPC中EMT的新机制之一,为鼻咽癌的治疗提供了新的靶点。

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