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Cancer Biol Ther. 2014 Oct;15(10):1404-12. doi: 10.4161/cbt.29923. Epub 2014 Jul 21.

Targeting HER3 with miR-450b-3p suppresses breast cancer cells proliferation.

Author information

1
Department of Oncology; The Affiliated Jiangyin Hospital of Southeast University Medical College; Wuxi, Jiangsu, PR China.
2
Department of Hematology; the First People's Hospital of Yunnan Province; Kunming, Yunnan, PR China.

Abstract

In breast cancer cells, heterodimerization of HER2 and HER3 plays important and dominant roles in the functionality and transformation of HER-mediated pathways, in particular the PI3K/Akt survival pathway. HER3 was considered as a major signaling hub in HER2-amplified cancers. Inhibition of HER3 expression may therefore represent a rational therapeutic approach to breast cancers where HER2/HER3-mediated signaling plays a role in tumorigenesis and progression. miRNAs exerts important roles in regulating gene expressions by binding to and repressing target mRNAs. Here we reported that miRNA-450b-3p inhibits HER3 expression by directly targeting 3' UTR of HER3 mRNA and represses the downstream signal transductions of HER family. Overexpression of miRNA-450b-3p in SKBR3 cells inhibits cells clonogenic potential and enhances their sensitivity to trastuzumab, a monoclonal antibody that binds to the HER2 receptor, or doxorubicin through repressing proliferative signal pathways mediated by HER3/HER2/PI3K/AKT. Furthermore, we found that breast cancer patients with tumors that demonstrating upregulated HER3 (> 2-fold) and downregulated miR-450b-3p (> 2-fold) expressions compared with the paired adjacent non-tumorous tissues showed significantly poorer overall survival (P<0.05). Our study identified miRNA-450b-3p as a new tumor repressor and also provided some evidences suggesting that downregulation of miR-450b-3p expression with concurrent overexpression of HER3 may serve as a prognostic biomarker for poor overall survival in breast cancer patients.

KEYWORDS:

HER3; breast cancer; miRNA-450b-3p

PMID:
25046105
PMCID:
PMC4130733
DOI:
10.4161/cbt.29923
[Indexed for MEDLINE]
Free PMC Article

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