Metformin mediates induction of miR-708 to inhibit self-renewal and chemoresistance of breast cancer stem cells through targeting CD47.
J Cell Mol Med
; 23(9): 5994-6004, 2019 09.
Article
em En
| MEDLINE
| ID: mdl-31273952
ABSTRACT
Breast cancer stem cells (BCSCs) have been considered responsible for cancer progression, recurrence, metastasis and drug resistance. However, the mechanisms by which cells acquire self-renewal and chemoresistance properties are remaining largely unclear. Herein, we evaluated the role of miR-708 and metformin in BCSCs, and found that the expression of miR-708 is significantly down-regulated in BCSCs and tumour tissues, and correlates with chemotherapy response and prognosis. Moreover, miR-708 markedly inhibits sphere formation, CD44+ /CD24- ratio, and tumour initiation and increases chemosensitivity of BCSCs. Mechanistically, miR-708 directly binds to cluster of differentiation 47 (CD47), and regulates tumour-associated macrophage-mediated phagocytosis. On the other hand, CD47 is essential for self-renewal, tumour initiation and chemoresistance of BCSCs, and correlates with the prognosis of breast cancer patients. In addition, the anti-type II diabetes drug metformin are found to be involved in the miR-708/CD47 signalling pathway. Therefore, our study demonstrated that miR-708 plays an important tumour suppressor role in BCSCs self-renewal and chemoresistance, and the miR-708/CD47 regulatory axis may represent a novel therapeutic mechanism of metformin in BCSCs.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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MicroRNAs
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Antígeno CD47
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Autorrenovação Celular
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Metformina
Limite:
Female
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Humans
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Middle aged
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article