GPR34 Stabilized by Deubiquitinase USP8 Suppresses Ferroptosis of ATC

G protein-coupled receptor 34 (GPR34) is an orphan receptor within the G protein-coupled receptor (GPCR) superfamily, and its specific role in anaplastic thyroid carcinoma (ATC) remains to be elucidated. In this study, we observed that GPR34 was aberrantly upregulated in ATC and the deletion of GPR3...

Full description

Saved in:
Bibliographic Details
Main Authors: Bokang Yan, Jiaxing Guo, Meiyuan Huang, Zhecheng Li, Jingyue Sun, Hailong Tan, Weiwei Lai, Shi Chang
Format: Article
Language:English
Published: Wiley 2025-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/mi/5576056
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849223064350359552
author Bokang Yan
Jiaxing Guo
Meiyuan Huang
Zhecheng Li
Jingyue Sun
Hailong Tan
Weiwei Lai
Shi Chang
author_facet Bokang Yan
Jiaxing Guo
Meiyuan Huang
Zhecheng Li
Jingyue Sun
Hailong Tan
Weiwei Lai
Shi Chang
author_sort Bokang Yan
collection DOAJ
description G protein-coupled receptor 34 (GPR34) is an orphan receptor within the G protein-coupled receptor (GPCR) superfamily, and its specific role in anaplastic thyroid carcinoma (ATC) remains to be elucidated. In this study, we observed that GPR34 was aberrantly upregulated in ATC and the deletion of GPR34 inhibited tumor progression both in vivo and in vitro. Additionally, suppression of GPR34 promoted ferroptosis in ATC cells. We further identified USP8 as a deubiquitinase (DUB) for GPR34, and the effects induced by GPR34 deletion were reversible through USP8 overexpression. Moreover, targeting USP8 with the inhibitor DUB-IN-3 effectively restrained ATC growth. Together, the present study revealed the role of GPR34 in ATC progression and ferroptosis, discovered its corresponding DUBs, and proposed GPR34 as a promising target for ATC therapy.
format Article
id doaj-art-106aed692eba46c98e1a83d77e8bfca0
institution Kabale University
issn 1466-1861
language English
publishDate 2025-01-01
publisher Wiley
record_format Article
series Mediators of Inflammation
spelling doaj-art-106aed692eba46c98e1a83d77e8bfca02025-08-26T00:00:06ZengWileyMediators of Inflammation1466-18612025-01-01202510.1155/mi/5576056GPR34 Stabilized by Deubiquitinase USP8 Suppresses Ferroptosis of ATCBokang Yan0Jiaxing Guo1Meiyuan Huang2Zhecheng Li3Jingyue Sun4Hailong Tan5Weiwei Lai6Shi Chang7Institute of Large-Scale Scientific Facility and Centre for Zero Magnetic Field ScienceDepartment of HematologyDepartment of PathologyDepartment of General SurgeryDepartment of PathologyDepartment of General SurgeryHunan Provincial Key Laboratory of Pediatric OrthopedicsNational Clinical Research Center for Geriatric DisordersG protein-coupled receptor 34 (GPR34) is an orphan receptor within the G protein-coupled receptor (GPCR) superfamily, and its specific role in anaplastic thyroid carcinoma (ATC) remains to be elucidated. In this study, we observed that GPR34 was aberrantly upregulated in ATC and the deletion of GPR34 inhibited tumor progression both in vivo and in vitro. Additionally, suppression of GPR34 promoted ferroptosis in ATC cells. We further identified USP8 as a deubiquitinase (DUB) for GPR34, and the effects induced by GPR34 deletion were reversible through USP8 overexpression. Moreover, targeting USP8 with the inhibitor DUB-IN-3 effectively restrained ATC growth. Together, the present study revealed the role of GPR34 in ATC progression and ferroptosis, discovered its corresponding DUBs, and proposed GPR34 as a promising target for ATC therapy.http://dx.doi.org/10.1155/mi/5576056
spellingShingle Bokang Yan
Jiaxing Guo
Meiyuan Huang
Zhecheng Li
Jingyue Sun
Hailong Tan
Weiwei Lai
Shi Chang
GPR34 Stabilized by Deubiquitinase USP8 Suppresses Ferroptosis of ATC
Mediators of Inflammation
title GPR34 Stabilized by Deubiquitinase USP8 Suppresses Ferroptosis of ATC
title_full GPR34 Stabilized by Deubiquitinase USP8 Suppresses Ferroptosis of ATC
title_fullStr GPR34 Stabilized by Deubiquitinase USP8 Suppresses Ferroptosis of ATC
title_full_unstemmed GPR34 Stabilized by Deubiquitinase USP8 Suppresses Ferroptosis of ATC
title_short GPR34 Stabilized by Deubiquitinase USP8 Suppresses Ferroptosis of ATC
title_sort gpr34 stabilized by deubiquitinase usp8 suppresses ferroptosis of atc
url http://dx.doi.org/10.1155/mi/5576056
work_keys_str_mv AT bokangyan gpr34stabilizedbydeubiquitinaseusp8suppressesferroptosisofatc
AT jiaxingguo gpr34stabilizedbydeubiquitinaseusp8suppressesferroptosisofatc
AT meiyuanhuang gpr34stabilizedbydeubiquitinaseusp8suppressesferroptosisofatc
AT zhechengli gpr34stabilizedbydeubiquitinaseusp8suppressesferroptosisofatc
AT jingyuesun gpr34stabilizedbydeubiquitinaseusp8suppressesferroptosisofatc
AT hailongtan gpr34stabilizedbydeubiquitinaseusp8suppressesferroptosisofatc
AT weiweilai gpr34stabilizedbydeubiquitinaseusp8suppressesferroptosisofatc
AT shichang gpr34stabilizedbydeubiquitinaseusp8suppressesferroptosisofatc