Li Zhongwei, Dong Meichen, Fan Dongmei, Hou Pingfu, Li Hongyuan, Liu Lingxia, Lin Cong, Liu Jiwei, Su Liangping, Wu Lan, Li Xiaoxue, Huang Baiqu, Lu Jun, Zhang Yu
The Key Laboratory of Molecular Epigenetics of Ministry of Education (MOE), Northeast Normal University, Changchun, China.
The Institute of Genetics and Cytology, Northeast Normal University, Changchun, China.
Oncotarget. 2017 Jun 27;8(40):67329-67343. doi: 10.18632/oncotarget.18622. eCollection 2017 Sep 15.
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 and . 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.
上皮-间质转化（EMT）是细胞可塑性的一个过程，对发育、分化、癌细胞迁移和肿瘤转移至关重要。作为一个经过充分研究的因子，转化生长因子-β（TGF-β）参与EMT，并涉及肿瘤进展的生理和病理功能。越来越多的证据表明，长链非编码RNA（lncRNA）在EMT和肿瘤转移中发挥关键作用。在此，我们发现lncRNA ANCR参与TGF-β1诱导的EMT。通过我们的染色质免疫沉淀（ChIP）和实时定量PCR分析，我们揭示TGF-β1通过增加HDAC3在ANCR启动子区域的富集来下调ANCR表达，这降低了ANCR启动子的H3和H4乙酰化水平。此外，通过蛋白质免疫印迹和Transwell分析，我们表明ANCR的异位表达部分减弱了TGF-β1诱导的EMT。在下游，ANCR通过降低RUNX2表达来抑制乳腺癌细胞迁移和乳腺癌转移。因此，我们的研究确定ANCR作为一种新的TGF-β下游分子，通过降低RUNX2表达对TGF-β1诱导的EMT至关重要。这些结果表明，ANCR可能成为乳腺癌的一个预后生物标志物和抗转移治疗靶点。
