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

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

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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 languageEnglish (US)
Pages (from-to)236-248
Number of pages13
JournalCell Adhesion and Migration
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

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

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