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PLoS One. 2012;7(6):e39520. doi: 10.1371/journal.pone.0039520. Epub 2012 Jun 25.

Antagonism of miR-21 reverses epithelial-mesenchymal transition and cancer stem cell phenotype through AKT/ERK1/2 inactivation by targeting PTEN.

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  • 1Department of Endocrine Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Abstract

BACKGROUND:

Accumulating evidence suggested that epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) characteristics, both of which contribute to tumor invasion and metastasis, are interrelated with miR-21. MiR-21 is one of the important microRNAs associated with tumor progression and metastasis, but the molecular mechanisms underlying EMT and CSC phenotype during miR-21 contributes to migration and invasion of breast cancer cells remain to be elucidated.

METHODOLOGY/PRINCIPAL FINDINGS:

In this study, MDA-MB-231/anti-miR-21 cells were established by transfected hsa-miR-21 antagomir into breast cancer MDA-MB-231 cells. EMT was evaluated by the changes of mesenchymal cell markers (N-cadherin, Vimentin, and alpha-SMA), epithelial cell marker (E-cadherin), as well as capacities of cell migration and invasion; CSC phenotype was measured using the changes of CSC surface markers (ALDH1 and CD44), and the capacity of sphereforming (mammospheres). We found that antagonism of miR-21 reversed EMT and CSC phenotype, accompanied with PTEN up-regulation and AKT/ERK1/2 inactivation. Interestingly, down-regulation of PTEN by siPTEN suppressed the effects of miR-21 antagomir on EMT and CSC phenotype, confirming that PTEN is a target of miR-21 in reversing EMT and CSC phenotype. The inhibitors of PI3K-AKT and ERK1/2 pathways, LY294002 and U0126, both significantly suppressed EMT and CSC phenotype, indicating that AKT and ERK1/2 pathways are required for miR-21 mediating EMT and CSC phenotype.

CONCLUSIONS/SIGNIFICANCE:

In conclusion, our results demonstrated that antagonism of miR-21 reverses EMT and CSC phenotype through targeting PTEN, via inactivation of AKT and ERK1/2 pathways, and showed a novel mechanism of which might relieve the malignant biological behaviors of breast cancer.

PMID:
22761812
[PubMed - indexed for MEDLINE]
PMCID:
PMC3382593
Free PMC Article
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