J Cancer 2015; 6(2):184-191. doi:10.7150/jca.10822 This issue Cite

Research Paper

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

Qiang Zhang1, Yonghui Yuan2, Jianchun Cui3, Tingting Xiao4, Daqing Jiang1✉

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

Citation:
Zhang Q, Yuan Y, Cui J, Xiao T, Jiang D. MiR-217 Promotes Tumor Proliferation in Breast Cancer via Targeting DACH1. J Cancer 2015; 6(2):184-191. doi:10.7150/jca.10822. https://www.jcancer.org/v06p0184.htm
Other styles

File import instruction

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, miR-217, breast cancer, proliferation, cell cycle


Citation styles

APA
Zhang, Q., Yuan, Y., Cui, J., Xiao, T., Jiang, D. (2015). MiR-217 Promotes Tumor Proliferation in Breast Cancer via Targeting DACH1. Journal of Cancer, 6(2), 184-191. https://doi.org/10.7150/jca.10822.

ACS
Zhang, Q.; Yuan, Y.; Cui, J.; Xiao, T.; Jiang, D. MiR-217 Promotes Tumor Proliferation in Breast Cancer via Targeting DACH1. J. Cancer 2015, 6 (2), 184-191. DOI: 10.7150/jca.10822.

NLM
Zhang Q, Yuan Y, Cui J, Xiao T, Jiang D. MiR-217 Promotes Tumor Proliferation in Breast Cancer via Targeting DACH1. J Cancer 2015; 6(2):184-191. doi:10.7150/jca.10822. https://www.jcancer.org/v06p0184.htm

CSE
Zhang Q, Yuan Y, Cui J, Xiao T, Jiang D. 2015. MiR-217 Promotes Tumor Proliferation in Breast Cancer via Targeting DACH1. J Cancer. 6(2):184-191.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License. See http://ivyspring.com/terms for full terms and conditions.
Popup Image