miR-720 inhibits tumor invasion and migration in breast cancer by targeting TWIST1
A partir d'une analyse de 105 échantillons tumoraux prélevés sur des patientes atteintes d'un cancer du sein, puis in vitro et in vivo, cette étude met en évidence des mécanismes par lesquels, en régulant de façon négative l'expression du gène TWIST1, le micro-ARN 720 inhibe les processus invasif et métastatique
Breast cancer is the leading cause of cancer death among females, with tumor metastasis being primarily responsible for breast cancer-associated mortality. Current literatures have shown that microRNAs are implicated in tumor metastasis. In this study, we found that the expression of miR-720 was significantly down-regulated in primary breast cancer, with greater down-regulation in metastatic tumors. Statistical analysis of 105 cases of primary human breast cancer demonstrated that decreased expression of miR-720 was correlated with lymph node metastasis. Furthermore, re-expression of miR-720 in breast cancer cells remarkably inhibited cell invasiveness and migration both in vitro and in vivo. Mechanistically, down-regulation of TWIST1, a promoter of metastasis that was identified as a direct functional target of miR-720, was attributed to the inhibition of metastasis. Consistent with the reduced TWIST1 levels in breast cancer, re-expression of mir-720 up-regulated epithelial markers (E-Cadherin and β-Catenin) and down-regulated mesenchymal markers (N-Cadherin, Fibronectin, Vimentin and MMP-2). Expression of miR-720 was inversely associated with TWIST1 in human breast cancer tissues. Knockdown of TWIST1 expression by siRNA exhibited similar effects to re-introduction of miR-720, whereas overexpression of TWIST1 (without the 3’-UTR) abrogated miR-720-mediated metastasis inhibition. Collectively, our data indicate that miR-720 is frequently decreased in breast cancer and manifests antimetastatic activity by down-regulating TWIST1, presenting a novel mechanism of microRNA-mediated regulation of tumor metastasis.
http://carcin.oxfordjournals.org/content/early/2013/10/01/carcin.bgt330.abstract