MiR-7 reduces the BCSC subset by inhibiting XIST to modulate the miR-92b/Slug/ESA axis and inhibit tumor growth.
BACKGROUND
Breast cancer stem cells (BCSCs) are typically seed cells of breast tumor that initiate and maintain tumor growth. MiR-7, as a cancer inhibitor, decreases the BCSC subset and inhibits tumor progression through mechanisms that remain unknown.


METHODS
We examined miR-7 expression in breast cancer and developed a BCSC-driven xenograft mouse model, to evaluate the effects of miR-7 overexpression on the decrease of the BCSC subset in vitro and in vivo. In addition, we determined how miR-7 decreased the BCSC subset by using the ALDEFLUOR, lentivirus infection, dual-luciferase reporter, and chromatin immunoprecipitation-PCR assays.


RESULTS
MiR-7 was expressed at low levels in breast cancer tissues compared with normal tissues, and overexpression of miR-7 directly inhibited lncRNA XIST, which mediates the transcriptional silencing of genes on the X chromosome, and reduced epithelium-specific antigen (ESA) expression by increasing miR-92b and inhibiting slug. Moreover, miR-7 suppressed CD44 and ESA by directly inhibiting the NF-κB subunit RELA and slug in breast cancer cell lines and in BCSC-driven xenografts, which confirmed the antitumor activity in mice injected with miR-7 agomir or stably infected with lenti-miR-7.


CONCLUSIONS
The findings from this study uncover the molecular mechanisms by which miR-7 inhibits XIST, modulates the miR-92b/Slug/ESA axis, and decreases the RELA and CD44 expression, resulting in a reduced BCSC subset and breast cancer growth inhibition. These findings suggest a potentially targeted treatment approach to breast cancer.
['Li|Miao|M|', 'Pan|Meng|M|', 'You|Chengzhong|C|', 'Zhao|Fengshu|F|', 'Wu|Di|D|', 'Guo|Mei|M|', 'Xu|Hui|H|', 'Shi|Fangfang|F|', 'Zheng|Danfeng|D|', 'Dou|Jun|J|']
D000818:Animals D001943:Breast Neoplasms D045744:Cell Line, Tumor D049109:Cell Proliferation D000071858:Epithelial Cell Adhesion Molecule D058750:Epithelial-Mesenchymal Transition D005260:Female D015972:Gene Expression Regulation, Neoplastic D006801:Humans D051379:Mice D016688:Mice, Inbred NOD D016513:Mice, SCID D035683:MicroRNAs D014411:Neoplastic Stem Cells D062085:RNA, Long Noncoding D000071250:Snail Family Transcription Factors D023041:Xenograft Model Antitumor Assays
miR-7 Subset Breast cancer Cancer stem cells lncRNA XIST