The Regulation and Function of miR-21-FOXO3a-miR-34b/c Signaling in Breast Cancer
AbstractUpregulation 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
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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.
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. International Journal of Molecular Sciences. 2015; 16(2):3148-3162.Chicago/Turabian Style
Liu, Xiangyan; Feng, Jie; Tang, Lili; Liao, Liqiu; Xu, Qing; Zhu, Shaihong. 2015. "The Regulation and Function of miR-21-FOXO3a-miR-34b/c Signaling in Breast Cancer." Int. J. Mol. Sci. 16, no. 2: 3148-3162.