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

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.
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
Journal	Cell adhesion & migration (Cell Adh Migr) Vol. 13 Issue 1 Pg. 236-248 (12 2019) ISSN: 1933-6926 [Electronic] United States
PMID	31240993 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References	CREB1 protein, human Cyclic AMP Response Element-Binding Protein MIRN200 microRNA, human MicroRNAs RNA, Messenger X-Linked Inhibitor of Apoptosis Protein XIAP protein, human
Topics	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, genetics) Neoplasm Invasiveness (genetics) RNA, Messenger (metabolism) Urinary Bladder Neoplasms (genetics, pathology) X-Linked Inhibitor of Apoptosis Protein (genetics)

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