乳腺癌是女性最常见的恶性肿瘤，其耐药性的形成是患者化疗失败的主要原因之一。肿瘤耐药是一个很复杂的过程，目前要在临床逆转耐药还存在诸多困难。已有报道表明miRNA参与调控细胞耐药。我们前期从髓性乳腺癌细胞BCap37出发，构建了两株耐药细胞，并通过miRNA芯片和miRNA文库技术筛出两个在亲代细胞和耐药细胞中差异表达的miRNA分子：miRNA-20a-5p及miRNA-106a-5p，二者属于同一家族，目前还未见二者调控乳腺癌耐药的报道。我们初步的实验结果表明二者的表达变化与临床乳腺癌病人的化疗效果显著相关，细胞实验也表明上调其表达可有效降低细胞对紫杉醇的耐药性，且二者联合作用有协同效果，但其作用机制以及其能否在体内逆转耐药还不清楚。因此我们拟综合利用多种生物实验技术，阐明该两个miRNA分子的作用靶点和相关的信号通路，考察其在体内逆转耐药的效果，为提高肿瘤化疗的效果提供可能的新的靶点。

Breast cancer is the most common malignancy in women. Drug Resistance is a major obstacle to the successful treatment of the patients with breast cancer. In addition to the P-gp-mediated multiple drug resistance, recent studies shown that a class of cell-derived RNA molecules (microRNA) might also be involved in the regulation of chemoresistance. To explore the possible roles and underlying mechanisms of micro-RNAs in drug resistance. We recently established two strains of breast cancer drug-resistant cell lines with paclitaxel, Bats-72, Bads-200 from Human myeloid breast tumor BCap37 cell. Subsequently, through miRNA array and miRNA library screening technology, we identified two miRNA molecules miRNA-20a-5p and miRNA-106a-5p. Further analyses demonstrated that these two microRNAs belong to the same family and the mechanisms of which in breast cancer chemoresistant progress have not been illustrated before. Preliminary results have demonstrated that the expressions of two miRNAs are highly corresponded with chemoresistant conditions in clinical breast cancer patients. The up-regulation of miRNA-20a-5p and miRNA-106a-5p can efficiently reduce the drug resistance to PTX in cytological experiments in vitro, and had synergy effect. However, whether they can reverse chemoresistance in vivo and their downstream target regions remains unknown. In this study, we will comprehensively utilize techniques of molecular biology, cytobiology, bioinformatics and laboratory animal science to illustrate the target region of two miRNAs and related signal pathway. The ability of miRNA-20a-5p and miRNA-106a-5p on reversing chemoresistance in vivo will be further studied for developing new strategies for targeted therapies in patients with chemoresistant breast cancer.