Hu Guinv, Zhao Xiaokang, Wang Jiang, Lv Liting, Wang Chaoqun, Feng Liang, Shen Liangqiong, Ren Weili
Department of Breast Surgery, Dongyang People's Hospital, Jinhua, Zhejiang 322100, P.R. China.
Department of Breast Surgery, Shaoxing Shangyu People's Hospital, Shaoxing, Zhejiang 312300, P.R. China.
Oncol Lett. 2018 Feb;15(2):1621-1629. doi: 10.3892/ol.2017.7476. Epub 2017 Nov 23.
MircroRNAs (miRNAs) are considered as essential regulators in the tumorigenesis and chemoresistance of multiple cancer types. In the present study, it was demonstrated that the expression levels of miR-125b were significantly downregulated in the tissues of patients with breast cancer (BC), as well as the BC cell lines . To study the association between chemoresistance and miR-125b in BC, doxorubicin (DOX)-resistant MCF-7 (MCF-7/R) cells were established, and gain- and loss-of-function experiments were performed. It was demonstrated that the overexpression of miR-125b increased the sensitivity of MCF-7/R cells to DOX. Furthermore, it was revealed that the sensitization of miR-125b mimics to DOX-induced cell death was regulated by the hematopoietic cell-specific protein 1-associated protein X-1 (HAX-1) vector and HAX-1 small interfering RNA. These results emphasized the notable function of miR-125b and its target of HAX-1 in regulating DOX-resistance. In addition, it was demonstrated that the miR-125b mimics promoted the loss of the mitochondrial membrane potential and the generation of reactive oxygen species induced by DOX treatment in MCF-7/R cells. These data suggest that the miR-125b-HAX-1-mitochondria pathway has a notable function in the treatment of DOX-resistant BC cells, which may provide a novel target for the chemotherapy of BC.
微小RNA（miRNA）被认为是多种癌症类型肿瘤发生和化疗耐药中的关键调节因子。在本研究中，已证实miR-125b在乳腺癌（BC）患者组织以及BC细胞系中的表达水平显著下调。为研究BC中化疗耐药与miR-125b之间的关联，建立了阿霉素（DOX）耐药的MCF-7（MCF-7/R）细胞，并进行了功能获得和功能缺失实验。结果表明，miR-125b的过表达增加了MCF-7/R细胞对DOX的敏感性。此外，还发现miR-125b模拟物对DOX诱导的细胞死亡的致敏作用受造血细胞特异性蛋白1相关蛋白X-1（HAX-1）载体和HAX-1小干扰RNA的调节。这些结果强调了miR-125b及其靶标HAX-1在调节DOX耐药中的显著作用。此外，还证实miR-125b模拟物促进了MCF-7/R细胞中DOX处理诱导的线粒体膜电位丧失和活性氧的产生。这些数据表明，miR-125b-HAX-1-线粒体途径在DOX耐药BC细胞的治疗中具有显著作用，这可能为BC化疗提供一个新的靶点。
