Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 236-248 |
| Number of pages | 13 |
| Journal | Cell Adhesion and Migration |
| Volume | 13 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2019 |
| Externally published | Yes |
Bibliographical note
Funding Information:This work was partially supported by grants from NIH/NCI [CA165980, CA177665, CA217923, CA229234], and NIH/NIEHS [ES000260]. We thank Dr. Mien-Chie Hung (The University of Texas MD Anderson Cancer Center, Houston, TX) for generous gift human miR-200c promoter luciferase reporter.
Publisher Copyright:
© 2019, © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
Keywords
- bladder cancer
- CREB inactivation
- invasion/metastasis
- mir-200c
- XIAP
