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J Cancer. 2015 Jan 1;6(2):184-91. doi: 10.7150/jca.10822. eCollection 2015.

MiR-217 Promotes Tumor Proliferation in Breast Cancer via Targeting DACH1.

Author information

1
1. Department of Breast Surgery, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning Province, 110042, China.
2
2. Department of Infection, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning Province, 110042, China.
3
3. Department of Endocrine Surgery, People's Hospital of Liaoning Province, Shenyang, Liaoning Province, 110042, China.
4
4. School of Chinese Medicine, Hong Kong Baptist University.

Abstract

OBJECTIVE:

The expression of DACH1 was frequently lost in human breast cancer, which significantly correlated with poor prognosis. Herein, we aim to investigate its underlying mechanisms.

METHODS:

The expression of miR-217 was detected by Taqman PCR. The mRNA and protein level of DACH1 were investigated by real time PCR and western blot. The dual-luciferase reporter system was used to determine the direct interaction between miR-217 and DACH1. A series of gain&loss of function assays were performed to measure the affects of miR-217 on tumor proliferation and cell cycle distribution.

RESULTS:

Compared to that in normal breast samples, the expression of miR-217 was significantly upregulated in breast cancer tissues. High level of miR-217 was notably correlated with highly histological grade, the triple negative subtype and advanced tumor stage. Moreover, the expression of miR-217 was negatively correlated with the expression of DACH1. The results of dual-luciferase reporter assay demonstrated that miR-217 directly targets and inhibits the transcriptive activity of DACH1. In vitro, treatment with miR-217 mimics significantly suppressed the proliferation of MCF-7 cells, induced G1 phase arrest and inhibited the expression of cyclin D1; while these effects were significantly reversed by the restoration of DACH1. In MDA-MB-231 cells, treatment with miR-217 inhibitors enhanced the cellular proliferation, promoted cell cycle progression and upregulated the expression of cyclin D1, which were neutralized by the pre-treatment of siRNA-DACH1. In vivo, inhibition of miR-217 significantly suppressed the xenografts growth and downregulated the expression of cyclin D1.

CONCLUSION:

We found that miR-217 was commonly overexpressed in breast cancer, which could enhance tumor proliferation via promoting cell cycle progression. Moreover, the DACH1 (the cell fate determination factor) was identified as a novel target of miR-217. Our results proposed inhibiting miR-217 to be a potent therapeutic strategy for breast cancer.

KEYWORDS:

DACH1; breast cancer; cell cycle; miR-217; proliferation

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