Role of deubiquitinase JOSD2 in the pathogenesis of esophageal squamous cell carcinoma  

作　　者：Wen-Peng Wang Dan Shi Duo Yun Jun Hu Jie-Fu Wang Jia Liu Yan-Peng Yang Ming-Rui Li Jun-FengWang Da-Lu Kong 

机构地区：[1]Department of Colorectal Oncology,Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Tianjin’s Clinical Research Center for Cancer,Key Laboratory of Cancer Prevention and Therapy,Tianjin 300060,China [2]Department of Gastrointestinal Surgery,Tianjin Nan Kai Hospital,Tianjin Medical University,Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair,Institute of Integrative Medicine for Acute Abdominal Diseases,Tianjin 300100,China [3]Department of Oncology,The First Hospital of Hohhot,Hohhot 010000,Inner Mongolia Autonomous Region,China [4]Department of Endocrinology,Dazhou Central Hospital,Dazhou 635000,Sichuan Province,China

出　　处：《World Journal of Gastroenterology》2024年第6期565-578,共14页世界胃肠病学杂志（英文版）

基　　金：Supported by Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-009A;Tianjin Medical University Cancer Hospital National Natural Science Foundation Cultivation Program,No.220108;National Natural Science Foundation of China,No.82373134;Science and Technology Development Fund of Tianjin Education Commission for Higher Education,No.2022KJ228;Chinese Anti-Cancer Association-Heng Rui Anti-angiogenesis Targeted Tumor Research Fund,No.2021001045;and Scientific Research Translational Foundation of Wenzhou Safety(Emergency)Institute of Tianjin University,No.TJUWYY2022025.

摘　　要：BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment options.Deubiquitinases(DUBs)have been confirmed to play a crucial role in the development of malignant tumors.JOSD2 is a DUB involved in con-trolling protein deubiquitination and influencing critical cellular processes in cancer.AIM To investigate the impact of JOSD2 on the progression of ESCC.METHODS Bioinformatic analyses were employed to explore the expression,prognosis,and enriched pathways associated with JOSD2 in ESCC.Lentiviral transduction was utilized to manipulate JOSD2 expression in ESCC cell lines(KYSE30 and RESULTS )Preliminary research indicated that JOSD2 was highly expressed in ESCC tissues,which was associated with poor prognosis.Further analysis demonstrated that JOSD2 was upregulated in ESCC cell lines compared to normal esophageal cells.JOSD2 knockdown inhibited ESCC cell activity,including proliferation and colony-forming ability.Moreover,JOSD2 knockdown decreased the drug resistance and migration of ESCC cells,while JOSD2 overexpression enhanced these phenotypes.In vivo xenograft assays further confirmed that JOSD2 promoted tumor proliferation and drug resistance in ESCC.Mechanistically,JOSD2 appears to activate the MAPK/ERK and PI3K/AKT signaling pathways.Mass spectrometry was used to identify crucial substrate proteins that interact with JOSD2,which identified the four primary proteins that bind to JOSD2,namely USP47,IGKV2D-29,HSP90AB1,and PRMT5.CONCLUSION JOSD2 plays a crucial role in enhancing the proliferation,migration,and drug resistance of ESCC,suggesting that JOSD2 is a potential therapeutic target in ESCC.

关 键 词：Esophageal squamous cell carcinoma JOSD2 UBIQUITINATION BIOMARKER Targeted therapy Drug resistance 

分 类 号：R735.1[医药卫生—肿瘤]