miR-181a-Twist1 pathway in the chemoresistance of tongue squamous cell carcinoma
miR-181a-Twist1 pathway in the chemoresistance of tongue squamous cell carcinoma
复制标题
miR-181a-Twist1 通路在舌鳞状细胞癌化疗耐药中的作用
DOI：
10.1016/j.bbrc.2013.10.051
复制
发表时间：
2013-11-15
影响因子：
3.1
通讯作者：
Wang, Anxun
中科院分区：
文献类型：
--
作者：
Liu, Mo;Wang, Jianguang;Wang, Anxun
虽然许多研究已经开始揭示化疗耐药的机制，但其机制仍不清楚。本研究旨在探讨miR-181 a-Twist 1通路在舌鳞癌化疗耐药中的作用。我们发现顺铂诱导的TSCC细胞系的化疗耐药性经历了EMT（上皮-间充质转化），并伴随着增强的转移潜力（体外迁移和侵袭），miR-181 a下调和Twist 1上调。功能分析表明，miR-181 a逆转了TSCC细胞的化疗耐药性，抑制了EMT和转移潜力。通过荧光素酶报告基因分析证实Twist 1是miR-181 a的直接靶基因。通过SiRNA敲减Twist 1导致TSCC细胞的化疗耐药性逆转、EMT抑制和转移潜力抑制。我们的研究表明miR-181 a-Twist 1通路可能在TSCC顺铂耐药、EMT和转移潜能增加中发挥重要作用。(C)2013 Elsevier Inc. All rights reserved.
Although many researches have been undertaken to disclose the mechanisms of chemoresistance, the mechanisms remain unclear. The aim of this study is to elucidate the role of miR-181a-Twist1 pathway in the chemoresistance of tongue squamous cell carcinoma (TSCC). We found that cisplatin-induced chemoresistance in TSCC cell lines underwent EMT (epithelial-mesenchymal transition) and was accompanied by enhancing metastatic potential (migration and invasion in vitro), miR-181a downregulation and Twist1 upregulation. Functional analyses indicated that miR-181a reversed chemoresistance, inhibited EMT and metastatic potential in TSCC cells. Twist1 was confirmed as a direct miR-181a target gene by luciferase reporter gene assays. Twist1 knockdown by siRNA led to a reversal of the chemoresistance, inhibited EMT and metastatic potential in TSCC cells. Our study demonstrates that miR-181a-Twist1 pathway may play an important role in the development of cisplatin-chemoresistance, with EMT and an increase the metastatic potential of TSCC cells. (C) 2013 Elsevier Inc. All rights reserved.