Title: Downregulation of miR-200c stabilizes XIAP mRNA and contributes to invasion and lung metastasis of bladder cancer.
Authors: Jin, Honglei; Xue, Lei; Mo, Lan; Zhang, Dongyun; Guo, Xirui; Xu, Jiheng; Li, Jingxia; Peng, Minggang; Zhao, Xuewei; Zhong, Minghao; Xu, Dazhong; Wu, Xue-Ru; Huang, Haishan; Huang, Chuanshu
Published In Cell Adh Migr, (2019 12)
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.
PubMed ID: 31240993
MeSH Terms: Animals; Cell Line, Tumor; Cell Movement/genetics; Cell Proliferation/genetics; Cyclic AMP Response Element-Binding Protein/metabolism; Down-Regulation/genetics; Gene Expression Regulation, Neoplastic/genetics; Humans; Lung Neoplasms/secondary*; Mice; Mice, Inbred C57BL; MicroRNAs/biosynthesis; MicroRNAs/genetics*; Neoplasm Invasiveness/genetics; RNA, Messenger/metabolism*; Urinary Bladder Neoplasms/genetics*; Urinary Bladder Neoplasms/pathology; X-Linked Inhibitor of Apoptosis Protein/genetics*