乳腺癌干细胞(BCSC)是导致乳腺癌不能根治而死亡的主要原因之一。本组前期研究发现miR-7在BCSC中低表达，过表达miR-7可通过下调癌基因SETDB1、抑制STAT3信号通路进而减低BCSC上皮间质转换及转移；并发现miR-7还可下调乳腺癌MDA-MB-231细胞系中BCSC亚群，但经何机制发挥该作用尚不清楚。本研究将在乳腺癌MDA-MB-231等细胞系和不同临床分期乳腺癌手术分离的细胞中通过慢病毒过表达miR-7，经流式细胞仪、qPCR、Western blot、荷乳腺癌NOD/SCID鼠及免疫组化等实验，检测ALDH1+细胞、BCSC亚群和HA、CD44、TGFβ1、Akt、mTOR等分子表达；探讨miR-7减低ALDH1A3并抑制CD44和TGFβ1表达而下调BCSC亚群的机制，为应用miR-7下调BCSC亚群靶向治疗乳腺癌提供新方法，对解决如何靶向治疗BCSC的难题有重要意义

The breast cancer stem cells (BCSCs) are one of the main reasons that result in the death of breast cancer patients due to without radical treatment of breast cancer. In our previous study, we found that the miR-7 was low expression in BCSCs detected by miRNA gene chips, and that the miR-7 overexpression significantly inhibited the expression of oncogene SETDB1, and reversed an epithelial-methsenchymal transition in MDA-MB-231 cells and BCSCs by downregulating STAT3 cell signaling. We also found that, from the previous study, the miR-7 overexpression could decrease the sub-population of BCSCs in MDA-MB-231 cell line, however, the mechanisms of leading to down-regulation of sub-population of BCSCs is poorly understood now. . In this study, we will infect the lenti-miR-7 into the MDA-MB-231, MCF-7 and BT549 cell lines as well as the cells isolated from the breast cancer patients sampled for excisional tumor tissues in different clinical stages, and detect the ALDH1+cells and BCSC sub-population by using FCM. Furthermore, we will test the molecular expression of HA, HAS2, CD44, TGF-β1, PI3K, Akt, mTOR, and SAMD2/3/7/ etc in the lenti-miR-7 infected breast cancer cell lines and the breast cancer patients’ samples as well as the breast cancer tissues isolated from the breast cancer bearing NOD/SCID mice that were injected with the BCSCs infected with lenti-miR-7 by using q-PCR, Western blot, breast cancer bearing NOD/SCID mice, and immunohistochemisty assays. The purpose of this study was to inquire into the molecular mechanisms of miR-7 down regulation of the sub-population of BCSCs via decrease of ALDH1A3 expression and inhibition of expression of CD44 and TGF-β1. The study achievement will have implications for therapeutic strategies that aim at targeting treatmet of highly invasive breast cancer by using the method of miR-7 overexpression. It has an important significant that we may solve the tough problem that is how to down regulate sub-population of BCSCs for radical treatment of the breast cancer.