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USP14去泛素化波形蛋白,而miR-320a调节USP14和波形蛋白,从而促进胃癌细胞的恶性发展。

USP14 de-ubiquitinates vimentin and miR-320a modulates USP14 and vimentin to contribute to malignancy in gastric cancer cells.

作者信息

Zhu Ying, Zhang Yan, Sui Zhenhua, Zhang Yi, Liu Min, Tang Hua

机构信息

Tianjin Life Science Research Center, Department of Pathogen Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, China.

出版信息

Oncotarget. 2017 Jul 25;8(30):48725-48736. doi: 10.18632/oncotarget.10706.

DOI:10.18632/oncotarget.10706
PMID:27448976
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5564720/
Abstract

Vimentin plays important roles in the epithelial-to-mesenchymal transition (EMT). In this study, we found that vimentin was highly expressed in human gastric cancer (GC) tissues and cell lines and significantly promoted cell growth, migration and invasion. Ubiquitin-specific protease 14 (USP14) interacted with the vimentin protein, which led to its de-ubiquitination. miR-320a was found to bind to the 3'UTR of both vimentin and USP14 transcripts and downregulate the expression of both proteins. The downregulation of miR-320a upregulates vimentin expression by directly binding to the 3'UTR of vimentin to derepress expression and indirectly by augmenting USP14 to increase vimentin stability in GC cells. Taken together, these results provide new insight into malignancy in gastric cancers.

摘要

波形蛋白在上皮-间质转化(EMT)中发挥重要作用。在本研究中,我们发现波形蛋白在人胃癌(GC)组织和细胞系中高表达,并显著促进细胞生长、迁移和侵袭。泛素特异性蛋白酶14(USP14)与波形蛋白相互作用,导致其去泛素化。发现miR-320a与波形蛋白和USP14转录本的3'UTR结合,并下调这两种蛋白的表达。miR-320a的下调通过直接结合波形蛋白的3'UTR以解除对其表达的抑制,以及通过增强USP14间接增加波形蛋白稳定性,从而上调GC细胞中波形蛋白的表达。综上所述,这些结果为胃癌的恶性进展提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f815/5564720/376f3e70f7f9/oncotarget-08-48725-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f815/5564720/c2a3d513d5ce/oncotarget-08-48725-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f815/5564720/c8735ae8e6c2/oncotarget-08-48725-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f815/5564720/ef2af3b573c9/oncotarget-08-48725-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f815/5564720/75b19de56b44/oncotarget-08-48725-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f815/5564720/376f3e70f7f9/oncotarget-08-48725-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f815/5564720/c2a3d513d5ce/oncotarget-08-48725-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f815/5564720/c8735ae8e6c2/oncotarget-08-48725-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f815/5564720/ef2af3b573c9/oncotarget-08-48725-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f815/5564720/75b19de56b44/oncotarget-08-48725-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f815/5564720/376f3e70f7f9/oncotarget-08-48725-g005.jpg

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