Data from TGF-β–Induced Upregulation of <i>malat1</i> Promotes Bladder Cancer Metastasis by Associating with suz12

Abstract

<div>Abstract<p><b>Purpose:</b> TGF-β promotes tumor invasion and metastasis by inducing an epithelial–mesenchymal transition (EMT). However, the underlying mechanisms causing this are not entirely clear. Long noncoding RNAs (lncRNA) have been shown to play important regulatory roles in cancer progression. The lncRNA <i>malat1</i> (<i>metastasis associated lung adenocarcinoma transcript 1</i>) is a critical regulator of the metastasis phenotype of lung cancer cells.</p><p><b>Experimental Design:</b> We, therefore, investigated whether TGF-β regulates <i>malat1</i> expression to promote tumor metastasis of bladder cancer. The expression levels of <i>malat1</i> and EMT markers were assayed in specimens of bladder cancer. The role of <i>malat1</i> in regulating bladder cancer metastasis was evaluated in cell and animal models.</p><p><b>Results:</b> TGF-β induces <i>malat1</i> expression and EMT in bladder cancer cells. <i>malat1</i> overexpression is significantly correlated with poor survival in patients with bladder cancer. <i>malat1</i> and E-cadherin expression is negatively correlated <i>in vitro</i> and <i>in vivo</i>. <i>malat1</i> knockdown inhibits TGF-β–induced EMT. <i>malat1</i> is associated with suppressor of zeste 12 (suz12), and this association results in decrease of E-cadherin expression and increase of N-cadherin and fibronectin expression. Furthermore, targeted inhibition of <i>malat1</i> or suz12 suppresses the migratory and invasive properties induced by TGF-β. Finally, we demonstrated that <i>malat1</i> or suz12 knockdown inhibits tumor metastasis in animal models.</p><p><b>Conclusion:</b> These data suggest that <i>malat1</i> is an important mediator of TGF-β–induced EMT, and suggest that <i>malat1</i> inhibition may represent a promising therapeutic option for suppressing bladder cancer progression. <i>Clin Cancer Res; 20(6); 1531–41. ©2014 AACR</i>.</p></div>