Research Papers:

Transforming growth factor-β1 promotes breast cancer metastasis by downregulating miR-196a-3p expression

Yan Chen, Shai Huang, Bo Wu, Jiankai Fang, Minsheng Zhu, Li Sun, Lifeng Zhang, Yongsheng Zhang, Maomin Sun, Lingling Guo and Shouli Wang _

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Oncotarget. 2017; 8:49110-49122. https://doi.org/10.18632/oncotarget.16308

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Yan Chen1,2,*, Shai Huang2,*, Bo Wu3,*, Jiankai Fang2, Minsheng Zhu2, Li Sun4, Lifeng Zhang1, Yongsheng Zhang5, Maomin Sun4, Lingling Guo2 and Shouli Wang2,6,7

1Department of Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China

2Department of Pathology, School of Biology & Basic Medical Sciences, Soochow University, Suzhou 215123, China

3Department of Surgery, The People’s Hospital of Sihong County, Sihong 223900, Jiangsu Province, China

4Laboratory Animal Research Center, Soochow University School of Medicine, Suzhou 215123, China

5Department of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China

6Laboratory of Molecular Pathology, Soochow University & Sihong County People’s Hospital, Suzhou 215123, China

7Suzhou Key Laboratory of Tumor Microenvironment and Pathology, Soochow University, Suzhou 215006, China

*These authors have contributed equally to this work

Correspondence to:

Shouli Wang, email: [email protected]

Lingling Guo, email: [email protected]

Keywords: microRNA, miR-196a-3p, transforming growth factor-β1, breast cancer

Received: December 12, 2016    Accepted: February 23, 2017    Published: March 17, 2017


Transforming growth factor-β1 is considered a key contributor to the progression of breast cancer. MicroRNAs are important factors in the development and progression of many malignancies. In the present study, upon studies of breast cancer cell lines and tissues, we showed that microRNA -196a-3p is decreased by transforming growth factor-β1 in breast cancer cells and associated with breast cancer progression. We identified neuropilin-2 as a target gene of microRNA -196a-3p and showed that it is regulated by transforming growth factor-β1. Moreover, transforming growth factor-β1-mediated inhibition of microRNA -196a-3p and activation of neuropilin-2were required for transforming growth factor-β1-induced migration and invasion of breast cancer cells. In addition, neuropilin-2 expression was suppressed in breast tumors, particularly in triple-negative breast cancers. Collectively, our findings strongly indicate that microRNA -196a-3p is a predictive biomarker of breast cancer metastasis and patient survival and a potential therapeutic target in metastatic breast cancer.

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