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Open AccessArticle

The Regulation and Function of miR-21-FOXO3a-miR-34b/c Signaling in Breast Cancer

1
Department of General Surgery, the Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha 410013, China
2
Department of Breast Surgery, the Xiangya Hospital, Central South University, 138 Tongzipo Road, Changsha 410013, China
3
Department of Nursing, Thomas Jefferson University, Philadelphia, PA 19107, USA
4
Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Jens Schlossmann
Int. J. Mol. Sci. 2015, 16(2), 3148-3162; https://doi.org/10.3390/ijms16023148
Received: 7 November 2014 / Revised: 13 January 2015 / Accepted: 27 January 2015 / Published: 30 January 2015
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells 2014)
Upregulation of miR-21 (microRNA-21) and downregulation of miR-34b/c have been found in breast cancer (BC). However, their regulation mechanism and function roles in BC have not been fully addressed. Here, we report that miR-21 levels were inversely correlated with miR-34b/c levels in BC. MiR-21 upregulation contributes to PTEN downregulation, which is beneficial for the activation of PI3K/AKT signaling. The activation of AKT phosphorylates FOXO3a, triggering relocalization of FOXO3a proteins from the nucleus to the cytoplasm. FOXO3a is a newly identified transcription factor responsible for miR-34b/c expression. Downregulation of nuclear FOXO3a decreased the expression levels of miR-34b and miR-34c in breast cancer cells, in which p53 was mutated. We also found upregulation of circulating miR-21 and downregulation of circulating miR-34b/c in BC patients’ serum. More importantly, we showed that systemic delivery of miR-34b/c or with anti-miR-21 significantly inhibited breast tumor growth in vivo. These results suggest that high circulating levels of miR-21 and low levels of miR-34b/c may provide potential biomarkers for BC diagnosis, and systemic delivery of miR-34b/c has potential as a therapeutic option for BC treatment. View Full-Text
Keywords: miR-21; miR-34b/c; FOXO3a; breast cancer; miRNAs injection miR-21; miR-34b/c; FOXO3a; breast cancer; miRNAs injection
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Liu, X.; Feng, J.; Tang, L.; Liao, L.; Xu, Q.; Zhu, S. The Regulation and Function of miR-21-FOXO3a-miR-34b/c Signaling in Breast Cancer. Int. J. Mol. Sci. 2015, 16, 3148-3162.

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