Journal
BIOMEDICINE & PHARMACOTHERAPY
Volume 79, Issue -, Pages 93-101Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2016.01.045
Keywords
microRNA-221/222; PTEN/Akt pathway; Cancer stem cell; Breast cancer
Funding
- National Natural Science Foundation of China [81172052]
- Dalian Medical University
- Liaoning Province innovative training project of college students
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Background: The miR-221/222 cluster has been discovered to function as oncogene in human malignancies including breast cancer. However, the role of miR-221/222 in the self-renewal of breast cancer stem cells (BCSCs) is not fully understood. In this study, we examined the impact and mechanism of miR-221/222 on the breast cancer cell viability, migration and invasion, and propagation of BCSCs. Methods: Human breast cancer cell line MCF-7 was transfected with miR-221/222 mimics or inhibitors to overexpress or knock down miR-221/222 respectively using Lipofactamine 2000. The biological effects of miR-221 and miR-222 were then assessed by cell proliferation assay, colony formation assay and transwell chamber assays. CD44/CD24 staining and mammosphere formation assay were performed to evaluate the ability of BCSCs self-renewal. Potential target gene phosphatase and tensin homolog (PTEN) and its downstream effector, phosphorylated Akt (p-Akt) were identified by Western blot and qRT-PCR methods. Results: PTEN, a tumor suppressor gene, was confirmed as a target of miR-221/222 in breast cancer cell line MCF-7. Downregulation of PTEN by miR-221/222 increased the phosphorylation of Akt. Enforced expression of miR-221/222 promoted breast cancer cell proliferation, migration and invasion via targeting PTEN/Akt pathway. Importantly, ectopic expression of miR-221/222 enriched the proportion of CD44+/CD24 BCSCs and improved the mammosphere formation capacity through targeting PTEN/Akt pathway. Blocking the endogenous miR-221/222 restored PTEN expression and subsequently decreased Akt phosphorylation, and thereby reversed this phenotype. Conclusions: Our results suggested that miR-221/222 enhance breast cancer growth, migration and invasion, meanwhile propagate the self-renewal of BCSCs. This is achieved possibly through targeting PTEN/Akt pathway. miR-221/222 might be a novel therapeutic candidate for human breast cancer. (C) 2016 Elsevier Masson SAS. All rights reserved.
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