USP5 promotes epithelial-mesenchymal transition by stabilizing SLUG in hepatocellular carcinoma

Theranostics
Jing MengCheng Yang

Abstract

Rationale: The role of SLUG in epithelial-mesenchymal transition during tumor progression has been thoroughly studied, but its precise regulation remains poorly explored. Methods: The affinity purification, mass spectrometry and CO-IP were performed to identify the interaction between SLUG and ubiquitin-specific protease 5 (USP5). Cycloheximide chase assays and deubiquitination assays confirmed that the effect of USP5 on the deubiquitin of SLUG. The dual-luciferase reporter and chromatin immunoprecipitation assays were employed to observe the direct transcriptional regulation of E-cadherin by SLUG effected by USP5. EMT related markers was detected by western blotting and immunofluorescence. Molecular docking, SPR sensor (biacore) and co-location were detected to prove Formononetin targets USP5. Bioinformatics analysis was used to study the relation of USP5 and SLUG to malignancy degree of HCC. Cell migration, invasion in HCC cells and xenografts model in nude mouse were conducted to detect the promotion of USP5 and the inhibition of Formononetin on EMT. Results: USP5 interacts with and stabilizes SLUG to regulate its abundance through USP5 deubiquitination activities in epithelial-mesenchymal transition (EMT) of hepatocellular ...Continue Reading

Citations

Sep 5, 2019·Cancer Metastasis Reviews·Julia MitschkeThomas Reinheckel
Nov 2, 2019·Essays in Biochemistry·Guillem LambiesVíctor M Díaz
Oct 6, 2020·Evidence-based Complementary and Alternative Medicine : ECAM·Zhulin WuLisheng Peng
Aug 2, 2020·Science China. Life Sciences·Xiaoyan DaiHongquan Zhang
Dec 22, 2019·Computational Biology and Chemistry·Yongyuan LiXianghui He
Jan 8, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hongwei LiuHaiyang Yu
Mar 5, 2021·Clinics and Research in Hepatology and Gastroenterology·Shimin Chen, Enfa Zhao
May 21, 2021·Drug Design, Development and Therapy·Gaoliang YanChengchun Tang
Oct 15, 2021·Journal of Medicinal Chemistry·Mandeep K MannMatthieu Schapira
Feb 2, 2022·Journal of Cellular Physiology·Weixiao HuangYan Chen

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Methods Mentioned

BETA
deubiquitination
Affinity purification
co-immunoprecipitation
xenograft
xenografts
ChIP
pulldown
ubiquitination
deubiquition
transfection

Software Mentioned

ChIPBASE
OPLS
LigPrep
GSEA
STORM

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