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

IF 3.3 3区 生物学 Q3 CELL BIOLOGY
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
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引用次数: 11

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.

Abstract Image

Abstract Image

Abstract Image

miR-200c下调可稳定XIAP mRNA,参与膀胱癌的侵袭和肺转移。
我们之前的研究表明,XIAP通过上调RhoGDIβ/MMP-2途径促进膀胱癌转移。然而,导致XIAP上调的分子机制尚不清楚。在目前的研究中,我们发现XIAP在人类高级别bc、高转移性bc和小鼠侵袭性bc中过表达。机制研究表明,XIAP在高转移性T24T细胞中的过表达是由于下调miR-200c介导XIAP mRNA稳定性增加所致。此外,miR-200c的下调是由于CREB失活,而miR-200c的下调减少了其与XIAP mRNA的3'-UTR区域的结合。总之,我们的研究结果证明了导致XIAP过表达的分子基础及其在BC侵袭中的关键作用。
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来源期刊
CiteScore
6.40
自引率
0.00%
发文量
7
审稿时长
53 weeks
期刊介绍: Cell Adhesion & Migration is a multi-disciplinary, peer reviewed open access journal that focuses on the biological or pathological implications of cell-cell and cell-microenvironment interactions. The main focus of this journal is fundamental science. The journal strives to serve a broad readership by regularly publishing review articles covering specific disciplines within the field, and by publishing focused issues that provide an overview on specific topics of interest within the field. Cell Adhesion & Migration publishes relevant and timely original research, as well as authoritative overviews, commentaries, and perspectives, providing context for the work presented in Cell Adhesion & Migration and for key results published elsewhere. Original research papers may cover all topics important in the field of cell-cell and cell-matrix interactions. Cell Adhesion & Migration also publishes articles related to cell biomechanics, biomaterial, and development of related imaging technologies.
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