title: MiR-217 Promotes Tumor Proliferation in Breast Cancer via Targeting DACH1.
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.
  
  
  CONCLUSIONS
  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.
authors: 1. Department of Breast Surgery, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning Province, 110042, China.
authors: Qiang
authors: Q
authors: Zhang
authors: 2. Department of Infection, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning Province, 110042, China.
authors: Yonghui
authors: Y
authors: Yuan
authors: 3. Department of Endocrine Surgery, People's Hospital of Liaoning Province, Shenyang, Liaoning Province, 110042, China.
authors: Jianchun
authors: J
authors: Cui
authors: 4. School of Chinese Medicine, Hong Kong Baptist University.
authors: Tingting
authors: T
authors: Xiao
authors: 1. Department of Breast Surgery, Liaoning Cancer Hospital & Institute, Shenyang, Liaoning Province, 110042, China.
authors: Daqing
authors: D
authors: Jiang
keywords: DACH1; breast cancer; cell cycle; miR-217; proliferation
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