LncRNA ANCR down-regulation promotes TGF-β-induced EMT and metastasis in breast cancer

// Zhongwei Li 1 , Meichen Dong 1 , Dongmei Fan 2 , Pingfu Hou 3 , Hongyuan Li 1 , Lingxia Liu 2 , Cong Lin 2 , Jiwei Liu 1 , Liangping Su 1 , Lan Wu 1 , Xiaoxue Li 2 , Baiqu Huang 2 , Jun Lu 2 and Yu Zhang 1 1 The Key Laboratory of Molecular Epigenetics of Ministry of Education (MOE), Northeast Normal University, Changchun, China 2 The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China 3 Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, China Correspondence to: Yu Zhang, email: zhangy288@nenu.edu.cn Keywords: lncRNA ANCR, TGF-β, EMT, RUNX2, metastasis Received: January 20, 2017      Accepted: May 29, 2017      Published: June 27, 2017 ABSTRACT Epithelial to mesenchymal transition (EMT) is a progression of cellular plasticity critical for development, differentiation, cancer cells migration and tumor metastasis. As a well-studied factor, TGF-β participates in EMT and involves in physiological and pathological functions of tumor progression. Accumulating evidence indicates that long noncoding RNAs(lncRNAs) play crucial roles in EMT and tumor metastasis. Here, we find that lncRNA ANCR participates in TGF-β1-induced EMT. By our ChIP and Real-time PCR assays, we reveal that TGF-β1 down-regulates ANCR expression by increasing HDAC3 enrichment at ANCR promoter region, which decreases both H3 and H4 acetylation of ANCR promoter. In addition, by western blot and transwell assays, we indicate that ectopic expression of ANCR partly attenuates the TGF-β1-induced EMT. Downstream, ANCR inhibits breast cancer cell migration and breast cancer metastasis by decreasing RUNX2 expression in vitro and in vivo . Thus, our study identifies ANCR, as a new TGF-β downstream molecular, is essential for TGF-β1-induced EMT by decreasing RUNX2 expression. These results implicate that ANCR might become a prognostic biomarker and an anti-metastasis therapy target for breast cancer.