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Int. J. Mol. Sci. 2015, 16(2), 3148-3162; doi:10.3390/ijms16023148

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
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)
View Full-Text   |   Download PDF [2916 KB, uploaded 30 January 2015]   |  

Abstract

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
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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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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