miR-218与口腔癌顺铂耐药性的相关性分析

本研究检测了顺铂敏感性和非敏感性口腔癌组织中的miR-218表达,发现在非敏感性口腔癌中miR-218的表达水平显著增加。本研究将人舌鳞状细胞癌细胞系(UM1)暴露在顺铂中6个月,发现miR-218在顺铂耐药的UM1细胞中明显上调。通过转染miR-218抑制剂可显著增加UM1细胞对顺铂的敏感性。转染miR-218模拟物可抑制PPP2R5A的表达。转染过表达PPP2R5A的慢病毒可增加UM1细胞对顺铂的敏感性。转染miR-218模拟物增强了UM1细胞活力,而转染过表达PPP2R5A的慢病毒则抑制了miR-218诱导的细胞活力。转染miR-218模拟物上调了β-catenin的表达,而转染过表达PPP2R5A的慢病毒则抑制了β-catenin的上调。本研究证明miR-218是口腔癌中顺铂耐药性的重要调节因子。miR-218的上调通过抑制PPP2R5A,从而激活Wnt信号通路,进而降低了口腔癌的顺铂敏感性。

Correlation between miR-218 and Cisplatin Resistance in Oral Cancer

This study examined the expression of miR-218 in cisplatin-sensitive and non-sensitive oral cancer tissues and found that the expression level of miR-218 was significantly increased in non-sensitive oral cancer.In addition,this study exposed human tongue squamous cell carcinoma cell line(UM1)to cisplatin for 6 months and found that miR-218 was significantly up-regulated in cisplatin-resistant UM1 cells.The sensitivity of UM1 cells to cisplatin was significantly increased by transfection of miR-218 inhibitors.Transfection of miR-218 mimics inhibited the expression of PPP2R5A.Transfection of PPP2R5A overexpressed lentivirus increased the sensitivity of UM1 cells to cisplatin.Transfection of miR-218 mimics enhanced UM1 cell viability,whereas transfection of PPP2R5A overexpressed lentivirus inhibited miR-218-induced cell viability.Transfection of miR-218 mimics up-regulated the expression ofβ-catenin,whereas transfection of PPP2R5A overexpressed lentivirus inhibited the up-regulation ofβ-catenin.This study demonstrates that miR-218 is an important regulator of cisplatin resistance in oral cancer.Up-regulation of miR-218 activates the Wnt signaling pathway by inhibiting PPP2R5A,thereby reducing the cisplatin sensitivity of oral cancer.