Inhibition of HAX-1 by miR-125a reverses cisplatin resistance in laryngeal cancer stem cells.
Inhibition of HAX-1 by miR-125a reverses cisplatin resistance in laryngeal cancer stem cells.
复制标题
DOI：
10.18632/oncotarget.13424
复制
发表时间：
2016-12-27
期刊：
影响因子：
--
通讯作者：
Yang X
中科院分区：
文献类型：
--
作者：
Liu J;Tang Q;Li S;Yang X
化疗耐药是喉癌化疗的主要障碍。最近，研究表明癌症干细胞是化疗失败的原因。此外，microRNA在肿瘤的发生、发展和多药耐药中发挥重要作用。在本研究中，我们发现microRNA-125 a在喉癌组织和Hep-2喉癌干细胞（Hep-2-CSCs）中的表达降低。MicroRNA-125 a功能获得性显著增加Hep-2-CSC对顺铂的体外和体内敏感性。与microRNA-125 a模拟物组合可以降低Hep-2-CSC对顺铂的半数最大抑制浓度。在机制上，我们发现microRNA-125 a通过靶向造血细胞特异性蛋白1相关蛋白X-1（HAX-1）逆转Hep-2-CSC中的顺铂耐药性。microRNA-125 a抑制HAX-1可通过线粒体途径促进顺铂诱导的Hep-2-CSC凋亡。此外，用microRNA-125 a模拟物转染细胞后，Hep-2-CSC对长春新碱、依托泊苷和阿霉素的多药耐药性大大提高。提示microRNA-125 a/HAX-1轴对喉癌化疗有促进作用。
Chemoresistance is a major obstacle in chemotherapy of laryngeal carcinoma. Recently, studies indicate that cancer stem cells are responsible for chemotherapy failure. In addition, microRNAs play important roles in tumor initiation, development and multidrug resistance. In the present study, we found that the expression of microRNA-125a was decreased in laryngeal carcinoma tissues and Hep-2 laryngeal cancer stem cells (Hep-2-CSCs). MicroRNA-125a gain-of-function significantly increased the sensitivity of Hep-2-CSCs to cisplatin in vitro and in vivo. Combination with microRNA-125a mimics can decrease the half maximal inhibitory concentration of Hep-2-CSCs to cisplatin. Mechanically, we found that microRNA-125a reverses cisplatin resistance in Hep-2-CSCs by targeting Hematopoietic cell-specific protein 1-associated protein X-1 (HAX-1). Inhibition of HAX-1 by microRNA-125a significantly promotes the cisplatin-induced apoptosis in Hep-2-CSCs through mitochondrial pathway. In addition, multidrug resistance of Hep-2-CSCs to vincristine, etoposide and doxorubicin was greatly improved after the cells were transfected with microRNA-125a mimics. These dates strongly suggested the promotion of microRNA-125a/HAX-1 axis on chemotherapy of laryngeal carcinoma.