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Ribosomal protein S3 mediates drug resistance of proteasome inhibitor: potential therapeutic application in multiple myeloma

文献类型：期刊论文

作者Chen, Gege3; Gao, Xuejie3; Jia, Xinyan3; Wang, Yingcong; Xu, Li3; Yu, Dandan; Chang, Shuaikang3; Deng, Hui3; Hu, Ke3; Wang, Guanli3
刊名HAEMATOLOGICA
出版日期2024-04-01
卷号109期号:4页码:1206-1219
ISSN号0390-6078
DOI10.3324/haematol.2023.282789
通讯作者Chen, Gege() ; Gao, Xuejie() ; Zhu, Weiliang(wlzhu@simm.ac.cn) ; Shi, Jumei(shijumei@tongji.edu.cn)
英文摘要Multiple myeloma (MM) remains incurable due to drug resistance. Ribosomal protein S3 (RPS3) has been identified as a non-Rel subunit of NF -KB. However, the detailed biological roles of RPS3 remain unclear. Here, we report for the first time that RPS3 is necessary for MM survival and drug resistance. RPS3 was highly expressed in MM, and knockout of RPS3 in MM inhibited cell growth and induced cell apoptosis both in vitro and in vivo. Overexpression of RPS3 mediated the proteasome inhibitor resistance of MM and shortened the survival of MM tumor -bearing animals. Moreover, our present study found an interaction between RPS3 and the thyroid hormone receptor interactor 13 (TRIP13), an oncogene related to MM tumorigenesis and drug resistance. We demonstrated that the phosphorylation of RPS3 was mediated by TRIP13 via PKC delta, which played an important role in activating the canonical NF -KB signaling and inducing cell survival and drug resistance in MM. Notably, the inhibition of NF -KB signaling by the small -molecule inhibitor targeting TRIP13, DCZ0415, was capable of triggering synergistic cytotoxicity when combined with bortezomib in drug -resistant MM. This study identifies RPS3 as a novel biomarker and therapeutic target in MM.
WOS关键词NF-KAPPA-B ; GENOMIC INSTABILITY ; PHOSPHORYLATION ; RPS3 ; APOPTOSIS ; DELTA
资助项目National Natural Science Foundation of China[82170200] ; National Natural Science Foundation of China[81900210] ; National Natural Science Foundation of China[82070224] ; National Natural Science Foundation of China[82000220] ; National Natural Science Foundation of China[81971529] ; Shanghai Sailing Program, China[21YF1435000]
WOS研究方向Hematology
语种英语
WOS记录号WOS:001197029900020
出版者FERRATA STORTI FOUNDATION
源URL[http://119.78.100.183/handle/2S10ELR8/310550]  
专题新药研究国家重点实验室
通讯作者Chen, Gege; Gao, Xuejie; Zhu, Weiliang; Shi, Jumei
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, CAS Key Lab Receptor Res,State Key Lab Drug Res, Shanghai, Peoples R China
2.Tongji Univ, Shanghai Peoples Hosp 10, Dept Hematol, Sch Med, Shanghai, Peoples R China
3.Tongji Univ, Shanghai East Hosp, Dept Hematol, Sch Med, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Gege,Gao, Xuejie,Jia, Xinyan,et al. Ribosomal protein S3 mediates drug resistance of proteasome inhibitor: potential therapeutic application in multiple myeloma[J]. HAEMATOLOGICA,2024,109(4):1206-1219.
APA Chen, Gege.,Gao, Xuejie.,Jia, Xinyan.,Wang, Yingcong.,Xu, Li.,...&Shi, Jumei.(2024).Ribosomal protein S3 mediates drug resistance of proteasome inhibitor: potential therapeutic application in multiple myeloma.HAEMATOLOGICA,109(4),1206-1219.
MLA Chen, Gege,et al."Ribosomal protein S3 mediates drug resistance of proteasome inhibitor: potential therapeutic application in multiple myeloma".HAEMATOLOGICA 109.4(2024):1206-1219.

入库方式： OAI收割

来源：上海药物研究所

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