Downregulation of miR-200c stabilizes XIAP mRNA and contributes to invasion and lung metastasis of bladder cancer

• Main Authors: Honglei Jin, Lei Xue, Lan Mo, Dongyun Zhang, Xirui Guo, Jiheng Xu, Jingxia Li, Minggang Peng, Xuewei Zhao, Minghao Zhong, Dazhong Xu, Xue-Ru Wu, Haishan Huang, Chuanshu Huang
• Format: Article
• Language: English
• Published: Taylor & Francis Group 2019-01-01
• Series: Cell Adhesion & Migration
• Subjects: xiap; mir-200c; bladder cancer; invasion/metastasis; creb inactivation
• Online Access: http://dx.doi.org/10.1080/19336918.2019.1633851
• ISSN: 1933-6918; 1933-6926

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.