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埃兹蛋白的抑制作用可抑制人鼻咽癌细胞的迁移和侵袭。

Inhibition of Ezrin suppresses cell migration and invasion in human nasopharyngeal carcinoma.

作者信息

Tang Yuanyuan, Sun Xiuzhen, Yu Shen, Bie Xu, Wang Jizhe, Ren Lidan

机构信息

Department of Otolaryngology Head and Neck Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China.

State Key Laboratory of Structural Analysis for Industrial Equipment, Dalian University of Technology, Dalian, Liaoning 116023, P.R. China.

出版信息

Oncol Lett. 2019 Jul;18(1):553-560. doi: 10.3892/ol.2019.10370. Epub 2019 May 17.

Abstract

Nasopharyngeal carcinoma (NPC) is one of the most severe types of malignant cancer of the head and neck as it is difficult to treat. Ezrin is highly expressed in numerous types of cancer. However, the role of Ezrin in NPC has not been fully investigated and further studies are required in order to uncover its therapeutic potential in the treatment of NPC. The aim of the present study was to investigate the expression of Ezrin in human NPC and to evaluate the effect of knockdown of Ezrin using small interfering (si)-RNA on NPC cell migration and invasion. The expression levels of Ezrin were determined using reverse transcription-quantitative polymerase chain reaction, immunohistochemical staining and western blotting. Following transfection of Ezrin-siRNA into NPC cells, cell invasion and migration were analyzed and the mRNA expression levels of matrix metalloproteinase(MMP)-2 and MMP9 were determined. The results revealed that the expression of Ezrin was markedly increased in human NPC tissue samples compared with normal adjacent nasopharyngeal tissue samples. Ezrin was also highly expressed in the NPC cell lines 6-10B and C6661 when compared with the normal nasopharyngeal cell line NP69. Transfection of NPC cell lines with siRNA targeting Ezrin significantly inhibited NPC cell migration and invasion, and downregulated the mRNA expression level of MMP2; however, no effect was observed on MMP9 mRNA expression. At the same time, knockdown of Ezrin significantly decreased the expression levels of phosphatidylinositol 3-kinase (PI3K) and phosphorylated protein kinase B (Akt), which downregulated the mRNA expression of MMP2. In conclusion, the results revealed that knockdown of Ezrin suppressed NPC migration and invasion by reducing the mRNA expression of MMP2 via the PI3K/Akt signaling pathway. These results highlight the important role of Ezrin in NPC cell migration and invasion. In addition, they indicate that silencing of Ezrin may serve as a potential therapeutic strategy to treat human NPC.

摘要

鼻咽癌(NPC)是头颈部最严重的恶性肿瘤类型之一,因其难以治疗。埃兹蛋白(Ezrin)在多种癌症中高表达。然而,Ezrin在鼻咽癌中的作用尚未得到充分研究,需要进一步研究以揭示其在鼻咽癌治疗中的潜在治疗价值。本研究的目的是研究Ezrin在人鼻咽癌中的表达,并评估使用小干扰(si)RNA敲低Ezrin对鼻咽癌细胞迁移和侵袭的影响。使用逆转录-定量聚合酶链反应、免疫组织化学染色和蛋白质印迹法测定Ezrin的表达水平。将Ezrin-siRNA转染到鼻咽癌细胞中后,分析细胞侵袭和迁移情况,并测定基质金属蛋白酶(MMP)-2和MMP9的mRNA表达水平。结果显示,与相邻正常鼻咽组织样本相比,Ezrin在人鼻咽癌组织样本中的表达显著增加。与正常鼻咽细胞系NP69相比,Ezrin在鼻咽癌细胞系6-10B和C6661中也高表达。用靶向Ezrin的siRNA转染鼻咽癌细胞系可显著抑制鼻咽癌细胞的迁移和侵袭,并下调MMP2的mRNA表达水平;然而,未观察到对MMP9 mRNA表达有影响。同时,敲低Ezrin可显著降低磷脂酰肌醇3激酶(PI3K)和磷酸化蛋白激酶B(Akt)的表达水平,从而下调MMP2的mRNA表达。总之,结果表明敲低Ezrin通过PI3K/Akt信号通路降低MMP2的mRNA表达,从而抑制鼻咽癌的迁移和侵袭。这些结果突出了Ezrin在鼻咽癌细胞迁移和侵袭中的重要作用。此外,它们表明沉默Ezrin可能作为治疗人类鼻咽癌的潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4bd9/6539485/23987cf3dd27/ol-18-01-0553-g00.jpg

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