a Nelson Institute of Environmental Medicine and Department of Environmental Medicine , New York University School of Medicine , Tuxedo , NY , USA.
b Department of Thoracic Surgery , Changzheng Hospital, Second Military Medical University , Shanghai , China.
Cell Adh Migr. 2019 Dec;13(1):236-248. doi: 10.1080/19336918.2019.1633851.
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.
我们之前的研究表明，XIAP 通过上调 RhoGDIβ/MMP-2 通路促进膀胱癌转移。然而，导致 XIAP 上调的分子机制尚不清楚。在目前的研究中，我们发现 XIAP 在人高分级膀胱癌、高转移性人膀胱癌和侵袭性小鼠膀胱癌中过度表达。机制研究表明，高转移性 T24T 细胞中 XIAP 的过表达是由于 XIAP 的 mRNA 稳定性增加，这是由 miR-200c 的下调介导的。此外，下调的 miR-200c 是由于 CREB 失活，而 miR-200c 的下调减少了其与 XIAP mRNA 3'-UTR 区域的结合。总之，我们的研究结果表明了导致 XIAP 过表达的分子基础及其在膀胱癌侵袭中的关键作用。
