USP8 promotes the tumorigenesis of intrahepatic cholangiocarcinoma via stabilizing OGT

USP8 promotes the tumorigenesis of intrahepatic cholangiocarcinoma via stabilizing OGT

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Abstract Ubiquitination was considered to be a crucial factor in intrahepatic cholangiocarcinoma (iCCA) development.Herein, we identified Ubiquitin-specific read more peptidase 8 (USP8) as a key regulator for promoting the tumorigenesis of iCCA cell via stabilizing OGT.USP8 was overexpressed in human tumor tissues and correlated with worse survival.Moreover, the mass spectrometry and co-immunoprecipitation analysis indicated that USP8 interacted with OGT.

USP8 worked as a bona fide deubiquitylase of OGT.It stabilized OGT in a deubiquitylation activity-dependent manner.Meanwhile, DUB-IN3, the USP8 inhibitor, could also restrain the malignancy of intrahepatic cholangiocarcinoma.In addition, USP8 depletion promoted the response of iCCA to pemigatinib.

In conclusion, our findings pointed to a previously undocumented catalytic role for USP8 as a deubiquitinating enzyme of OGT.The USP8-OGT axis could be a potential target for iphone 14 price texas iCCA therapy.