Molecular Therapy: Oncolytics | 卷:18 |
miR-7 Reduces Breast Cancer Stem Cell Metastasis via Inhibiting RELA to Decrease ESAM Expression | |
Jun Dou1  Jing Wang2  Fengshu Zhao3  Danfeng Zheng4  Chengzhong You5  Mei Guo6  Miao Li6  Ling Wang6  Di Wu6  Meng Pan6  Hui Xu6  | |
[1] Department of Gynecology & | |
[2] Jiangsu Province Hospital, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; | |
[3] Obstetrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China; | |
[4] Department of General Surgery, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, China; | |
[5] Department of Pathogenic Biology and Immunology, School of Medicine, Southeast University, Nanjing 210009, China; | |
关键词: breast cancer; miR-7; breast cancer stem cells; endothelial cell-selective adhesion molecule; endothelial cell-selective adhesion molecule(ESAM); metastasis; | |
DOI : | |
来源: DOAJ |
【 摘 要 】
This study aimed to present evidence that miR-7 inhibited the metastasis of breast cancer stem cells (BCSCs) and elucidated the mechanisms that have remained unknown. The samples collected from miR-7 agomir-treated, BCSC-driven tumors were subjected to a protein array to analyze the protein expression profiles. A dual-luciferase reporter and chromatin immunoprecipitation-PCR were used to validate and evaluate the molecular expressions of interest in the collected breast cancer tissues and cell lines. miR-7 overexpression affecting metastasis of BCSCs was further evaluated in mice. The endothelial cell-selective adhesion molecule (ESAM) was highly expressed in breast cancer tissues and in BCSC-driven xenografts. Results of the dual-luciferase reporter and chromatin immunoprecipitation-PCR indicated that the miR-7 mimic reduced RELA expression by directly targeting the 3′ UTR of RELA to inhibit ESAM expression in MDA-MB-231 cells. Moreover, the expression levels of RELA, CD44, and ESAM were significantly decreased in lentivirus (Lenti)-miR-7-BCSC-driven xenografts compared with the control xenografts, accompanied with an increase in E-cadherin and a decrease in vimentin expression, as well as reduction in tumor growth and metastasis to lungs. Our data demonstrated that miR-7 overexpression reduced the metastasis of BCSCs via inhibiting ESAM, suggesting that ESAM could be a potential target for breast cancer therapy.
【 授权许可】
Unknown