Journal
CANCERS
Volume 11, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/cancers11030344
Keywords
WP1130; TRAIL; c-FLIP; DR5; MicroRNA
Categories
Funding
- NRF - Korea Government (MSIP) [2014R1A5A2010008, NRF-2018R1D1A3B07049596, NRF-2017R1D1A1B03028366]
Ask authors/readers for more resources
WP1130, a partially selective deubiquitinases (DUB) inhibitor, inhibits the deubiquitinating activities of USP5, USP9X, USP14, USP37, and UCHL1. In this study, we investigate whether WP1130 exerts sensitizing effect on TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human renal carcinoma cells. Combinations of WP1130 and TRAIL significantly induced apoptosis in renal carcinoma, lung carcinoma and hepatocellular carcinoma cells, but not in normal cells (human mesangial cells (MC) and normal mouse kidney cells (TCMK-1)). The downregulation of c-FLIP protein expression was involved in combined treatment-induced apoptosis. WP1130-induced c-FLIP downregulation was regulated by microRNA (miR)-708 upregulation via inhibition of USP9X. Interestingly, knockdown of USP9X markedly induced c-FLIP downregulation, upregulation of miR-708 expression and sensitivity to TRAIL. Furthermore, ectopic expression of USP9X prevented c-FLIP downregulation and apoptosis upon combined treatment. In sum, WP1130 sensitized TRAIL-induced apoptosis through miR-708-mediated downregulation of c-FLIP by inhibition of USP9X.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available