miR-7 Reduces Breast Cancer Stem Cell Metastasis via Inhibiting RELA to Decrease ESAM Expression

Molecular Therapy: Oncolytics

卷:18

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