PSMD2-Mediated MAPK Signaling Promotes Bladder Cancer Development and Immune Microenvironment RemodelingOA
Objectives:Bladder cancer(BCa)progression is closely linked to the immune microenvironment.However,the key molecules that regulate this microenvironment and their specific mechanisms remain poorly understood.This study aims to identify a key molecule and elucidate its mechanisms,providing a theoretical basis for identifying novel therapeutic targets.Methods:Immune microenvironment-related genes in BCa were identified using The Cancer Genome Atlas and Shanghai Tenth People’s Hospital datasets.Proteasome 26S subunit non-ATPase 2(PSMD2)expression was validated via quantitative polymerase chain reaction(qPCR),Western blot(WB)analysis,and immunofluorescence(IF).In vitro and in vivo experiments confirmed the role of PSMD2 in cell proliferation,invasion,and migration.Kyoto encyclopedia of genes and genomes(KEGG)and Gene Ontology(GO)analyses were conducted to assess PSMD2’s influence on immune microenvironment remodeling.A pathomics model predicted PSMD2 expression in patients with BCa.Results:PSMD2 was identified as a critical factor in BCa,with high expression correlating with poor prognosis and tumor progression.Mechanistically,PSMD2 enhances malignancy by promoting mitogen-activated protein kinase kinase(MEK)and extracellular signal-regulated kinase(ERK)phosphorylation within the mitogen-activated protein kinase(MAPK)signaling pathway.Combined bioinformatics and experimental analyses reveal that PSMD2 downregulates chemokine(C-X-C motif)ligand 14(CXCL14)expression and secretion via the MAPK pathway,thereby remodeling the immune microenvironment and driving tumor progression.Pathomics analysis further supports the potential of PSMD2 expression as a predictive marker in BCa tissues.Conclusion:PSMD2 is overexpressed in BCa and significantly correlates with poor prognosis and tumor progression.It promotes malignant development and immune microenvironment remodeling through the MAPK pathway.Pathological analysis can predict PSMD2 expression,offering valuable insights into immunotherapy responses and survival outcomes.
Shuwen Sun;Jingcheng Zhang;Zongtai Zheng;Yajuan Hao;Tianyuan Xu;Ji Liu;Liang Sun;Aimin Wang;Yadong Guo;Shiyu Mao;Xu Zhang;Yunfei Xu;Yifan Chen;Yang Yan
Department of Urology,Shanghai Tenth People’s Hospital,School of Medicine,Tongji University,Shanghai,200072,China Department of Urology,Bengbu First People’s Hospital,Bengbu,233000,China Urologic Cancer Institute,School of Medicine,Tongji University,Shanghai,200072,China Department of Nuclear Medicine,Shanghai Tenth People’s Hospital,School of Medicine,Tongji University,Shanghai,200072,ChinaDepartment of Urology,Shanghai Tenth People’s Hospital,School of Medicine,Tongji University,Shanghai,200072,China Department of Urology,Bengbu First People’s Hospital,Bengbu,233000,China Urologic Cancer Institute,School of Medicine,Tongji University,Shanghai,200072,ChinaDepartment of Urology,The Affiliated Guangdong Second Provincial General Hospital of Jinan University,Guangzhou,510317,ChinaDepartment of Urology,Shanghai Tenth People’s Hospital,School of Medicine,Tongji University,Shanghai,200072,China Urologic Cancer Institute,School of Medicine,Tongji University,Shanghai,200072,ChinaDepartment of Urology,Shanghai Tenth People’s Hospital,School of Medicine,Tongji University,Shanghai,200072,China Department of Urology,Bengbu First People’s Hospital,Bengbu,233000,China Urologic Cancer Institute,School of Medicine,Tongji University,Shanghai,200072,ChinaDepartment of Urology,Shanghai Tenth People’s Hospital,School of Medicine,Tongji University,Shanghai,200072,China Urologic Cancer Institute,School of Medicine,Tongji University,Shanghai,200072,ChinaDepartment of Urology,Bengbu First People’s Hospital,Bengbu,233000,ChinaDepartment of Urology,Bengbu First People’s Hospital,Bengbu,233000,ChinaDepartment of Urology,Shanghai Tenth People’s Hospital,School of Medicine,Tongji University,Shanghai,200072,China Urologic Cancer Institute,School of Medicine,Tongji University,Shanghai,200072,ChinaDepartment of Urology,Shanghai Tenth People’s Hospital,School of Medicine,Tongji University,Shanghai,200072,China Urologic Cancer Institute,School of Medicine,Tongji University,Shanghai,200072,ChinaBio-X Institutes(Key Laboratory for the Genetics of Development and Neuropsychiatric Disorders),Shanghai Jiao Tong University,Shanghai,200240,ChinaDepartment of Urology,Shanghai Tenth People’s Hospital,School of Medicine,Tongji University,Shanghai,200072,China Urologic Cancer Institute,School of Medicine,Tongji University,Shanghai,200072,ChinaDepartment of Urology,Shanghai Tenth People’s Hospital,School of Medicine,Tongji University,Shanghai,200072,China Department of Urology,Bengbu First People’s Hospital,Bengbu,233000,China Urologic Cancer Institute,School of Medicine,Tongji University,Shanghai,200072,ChinaDepartment of Urology,Shanghai Tenth People’s Hospital,School of Medicine,Tongji University,Shanghai,200072,China Department of Urology,Bengbu First People’s Hospital,Bengbu,233000,China Urologic Cancer Institute,School of Medicine,Tongji University,Shanghai,200072,China
医药卫生
Bladder cancer(BCa)proteasome 26S subunit non-ATPase 2(PSMD2)C-X-C motif chemokine ligand 14(CXCL14)immune infiltration
《Oncology Research》 2026 (4)
P.736-759,24
supported by the National Natural Science Foundation of China Commission,Youth Project(No.82203150,No.82302304)Anhui Health Commission Research Project(No.2024Aa30184)The Bengbu City Health and Medical Research Project(BBWK2024A103)Cultivation grant for clinical and basic integration research of Shanghai Tenth People’s Hospital(SYYYRH2025020)Doctoral Workstation Foundation of Guangdong Second Provincial General Hospital,China(Grant No.2022BSGZ011)Elevate Engineering Foundation of Guangdong Second Provincial General Hospital,China(Grant No.TJGC2022009)Science and Technology Program of Guangzhou,China(2024A04J4159)China Postdoctoral Science Foundation(2021M702137)Natural Science Foundation of Chongqing(cstc2021jcyj-msxmX1176)Chongming District Sustainable Development Science and Technology Innovation Initiative Project(CKY2022-30).
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