MicroRNAs contribute to the chemoresistance of cisplatin in tongue squamous cell carcinoma lines
MicroRNAs contribute to the chemoresistance of cisplatin in tongue squamous cell carcinoma lines
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MicroRNA 有助于舌鳞状细胞癌细胞系中顺铂的化疗耐药性。
DOI：
10.1016/j.oraloncology.2010.02.002
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发表时间：
2010-04-01
期刊：
影响因子：
4.8
通讯作者：
Zhang, Chen-ping
中科院分区：
文献类型：
--
作者：
Yu, Zhi-wei;Zhong, Lai-ping;Zhang, Chen-ping
microRNAs（miRNAs）是一类非编码的小分子RNA，是基因表达的负调控因子。它们与人类癌症密切相关，包括口腔鳞状细胞癌（OSCC）。miRNAs参与口腔鳞癌化疗敏感性和耐药性的重要调节因子的证据尚不清楚。本研究首次采用miRNA芯片技术比较舌鳞癌顺铂敏感株（Tca 8113）及其顺铂耐药株（Tca/cisplatin）的miRNA表达差异。通过miRNAs实时定量PCR验证miR-21、-214和-23a三种miRNAs，并通过抗miRNAs寡核苷酸（miR-214和-23a）和前体miRNAs质粒转染（miR-21）进行干预。进一步研究了miR-23 a和DNA拓扑异构酶II β（TOP 2B）与顺铂化疗耐药性的关系。在Tca 8113和Tca/cisplatin细胞之间的480个差异miRNAs中，有19个差异。发现miR-214和-23a在Tca/顺铂细胞中随着对顺铂的化学抗性而增加，而发现miR-21在Tca/顺铂细胞中随着对顺铂的化学敏感性而降低。这三种miRNAs的干预可以降低Tca/cisplatin细胞对顺铂的耐药性。反义miR-23 a转染Tca/cisplatin细胞后，TOP 2B蛋白表达增加。我们的研究结果表明，顺铂敏感和耐药的舌鳞状细胞癌细胞系之间存在差异的miRNA与化疗敏感性和耐药性。在舌鳞状细胞癌细胞系中，miR-21作为化学敏感性miRNA，而miR-214和-23a作为化学抗性miRNA。miR-23 a是TOP 2B的上游调节因子，实现顺铂的耐药。(C)2010爱思唯尔有限公司版权所有。
MicroRNAs (miRNAs) are small non-coding RNAs that function as negative regulators of gene expression. They are strongly implicated in human cancers, including oral squamous cell carcinoma (OSCC). Evidence for the involvement of miRNAs as important regulators of chemosensitivity and chemoresistance in OSCC is not well understood. In this study, miRNA microarray was firstly used to compare the differential miRNAs levels between the cisplatin-sensitive tongue squamous cell carcinoma line (Tca8113) and its cisplatin-resistant subline(Tca/cisplatin). Three miRNAs of miR-21, -214, and -23a were validated by miRNAs real-time PCR, and intervened by anti-miRNA oligonucleotides (miR-214 and -23a) and pre-miRNA plasmid transfection (miR-21). Further relationship between miR-23a and DNA topoisomerase II beta (TOP2B) on the chemoresistance against cisplatin was studied. There were 19 out of 480 differential miRNAs between the Tca8113 and Tca/cisplatin cells. miR-214 and -23a were found increased as with chemoresistance against cisplatin in the Tca/cisplatin cells while miR-21 was found decreased as with chemosensitivity for cisplatin in the Tca/cisplatin cells. Intervention of these three miRNAs could decrease the chemoresistance against cisplatin in Tca/cisplatin cells. Transfection of anti-miR-23a into the Tca/cisplatin cells could increase the TOP2B protein expression. Our results suggest the existence of differential miRNAs with chemosensitivity and chemoresistance between the cisplatin-sensitive and resistant tongue squamous cell carcinoma lines. miR-21 serves as a chemosensitive miRNA, while miR-214 and -23a serve as chemoresistant miRNAs in the tongue squamous cell carcinoma lines. miR-23a is an up-stream regulator of TOP2B to realize the chemoresistance of cisplatin. (C) 2010 Elsevier Ltd. All rights reserved.