Research Papers:

MicroRNA-1229 overexpression promotes cell proliferation and tumorigenicity and activates Wnt/β-catenin signaling in breast cancer

Zhanyao Tan, Haiqing Zheng, Xiangxia Liu, Wenhui Zhang, Jinrong Zhu, Geyan Wu, Lixue Cao, Junwei Song, Shu Wu, Libing Song and Jun Li _

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Oncotarget. 2016; 7:24076-24087. https://doi.org/10.18632/oncotarget.8119

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Zhanyao Tan1,2,*, Haiqing Zheng3,*, Xiangxia Liu4,*, Wenhui Zhang5, Jinrong Zhu1, Geyan Wu1, Lixue Cao1, Junwei Song1, Shu Wu2, Libing Song2, Jun Li1

1Program of cancer research, Affiliated Guangzhou Women and Children’s Hospital, Zhongshan School of Medicine, Sun Yat-Sen University

2State Key Laboratory of Oncology in Southern China, Department of Experimental Research, Sun Yat-sen University Cancer Center

3Department of Rehabilitation Medicine, The third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

4Department of Plastic Surgery, The First Affiliated Hospital of Sun Yat-sen University

5Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University

*These authors have contributed equally to this work

Correspondence to:

Jun Li, e-mail: lijun37@mail.sysu.edu.cn

Libing Song, e-mail: songlb@sysucc.org.cn

Keywords: MiR-1229, breast cancer, proliferation, Wnt/β-catenin pathway

Received: December 12, 2015    Accepted: March 01, 2016    Published: March 16, 2016


Constitutive activation of the Wnt/β-catenin pathway promotes malignant proliferation and it is inversely correlated with the prognosis of patients with breast cancer. However, mutations in key regulators, such as APC, Axin and β-catenin, contribute to aberrant activation of the Wnt/β-catenin signaling pathway in various cancers, but rarely found in breast cancer, suggesting that other mechanisms might be involved in the activation of Wnt/β-catenin signaling in breast cancer. In the present study, we found that miR-1229 expression was markedly upregulated in breast cancer and associated with poor survival. Overexpressing miR-1229 promoted while inhibiting miR-1229 reduced, proliferation of breast cancer cell proliferation in vitro and tumor growth in vivo. Furthermore, we found that overexpression of miR-1229 activated the Wnt/β-catenin signaling pathway in breast cancer by directly targeting the multiple important negative regulators of Wnt/β-catenin signaling, including adenomatous polyposis coli (APC), glycogen synthase kinase-3β (GSK-3β), and inhibitor of β-catenin and T cell factor (ICAT). Taken together, our results suggest that miR-1229 plays an important role in promotion breast cancer progression and may represent a novel therapeutic target in breast cancer.

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