Our previous studies have demonstrated that XIAP promotes bladder cancer metastasis through upregulating RhoGDIβ/MMP-2 pathway. However, the molecular mechanisms leading to the XIAP upregulation was unclear. In current studies, we found that XIAP was overexpressed in human high grade BCs, high metastatic human BCs, and in mouse invasive BCs. Mechanistic studies indicated that XIAP overexpression in the highly metastatic T24T cells was due to increased mRNA stability of XIAP that was mediated by downregulated miR-200c. Moreover, the downregulated miR-200c was due to CREB inactivation, while miR-200c downregulation reduced its binding to the 3'-UTR region of XIAP mRNA. Collectively, our results demonstrate the molecular basis leading to XIAP overexpression and its crucial role in BC invasion.

中文翻译：

---

miR-200c的下调可稳定XIAP mRNA，并有助于膀胱癌的侵袭和肺转移。

我们以前的研究表明，XIAP通过上调RhoGDIβ/ MMP-2途径促进膀胱癌转移。但是，导致XIAP上调的分子机制尚不清楚。在当前的研究中，我们发现XIAP在人类高级BC，高转移性人类BC和小鼠浸润性BC中过表达。机理研究表明，XIAP在高转移性T24T细胞中的过度表达是由于XIAP的mRNA稳定性增加，这是由下调的miR-200c介导的。而且，miR-200c的下调是由于CREB失活，而miR-200c的下调则降低了其与XIAP mRNA 3'-UTR区的结合。总的来说，我们的结果证明了导致XIAP过表达的分子基础及其在BC侵袭中的关键作用。