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

// Yan Chen 1, 2, * , Shai Huang 2, * , Bo Wu 3, * , Jiankai Fang 2 , Minsheng Zhu 2 , Li Sun 4 , Lifeng Zhang 1 , Yongsheng Zhang 5 , Maomin Sun 4 , Lingling Guo 2 and Shouli Wang 2, 6, 7 1 Department of Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China 2 Department of Pathology, School of Biology & Basic Medical Sciences, Soochow University, Suzhou 215123, China 3 Department of Surgery, The People’s Hospital of Sihong County, Sihong 223900, Jiangsu Province, China 4 Laboratory Animal Research Center, Soochow University School of Medicine, Suzhou 215123, China 5 Department of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China 6 Laboratory of Molecular Pathology, Soochow University & Sihong County People’s Hospital, Suzhou 215123, China 7 Suzhou 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: wangsoly112@hotmail.com Lingling Guo, email: guo-lingling@126.com Keywords: microRNA, miR-196a-3p, transforming growth factor-β1, breast cancer Received: December 12, 2016     Accepted: February 23, 2017     Published: March 17, 2017 ABSTRACT 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.