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SPAG5 as a novel biomarker and potential therapeutic target via regulating AKT pathway in multiple myeloma

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机构: [1]Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China [2]Department of General Practice, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China [3]Department of General Practice, Xinrui Hospital of Xinwu District, Wuxi (Wuxi Branch of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine), Jiangsu, China [4]Hongqiao International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Basic Medicine, Chemical Biology Division of Shanghai Universities E-Institutes, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education/Shanghai Jiao Tong University, Research Units of Stress and Tumor (2019RU043), Chinese Academy of Medical Sciences, School of Medicine, Shanghai, People’s Republic of China
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关键词: Multiple myeloma SPAG5 biomarker AKT

摘要:
SPAG5, as a spindle-associated protein in mitosis, has been observed to have oncogenic activities in solid tumors. Here, we identified that SPAG5 expression was correlated with the deterioration of plasma cell malignancy and SPAG5 overexpression (OE) predicted unfavorable outcomes in multiple myeloma (MM). SPAG5 knockdown led to anti-MM effects in MM cell lines and animal xenograft models by regulating cell growth and apoptosis. Furthermore, gene set enrichment analysis (GSEA) revealed that PI3K/AKT/mTOR pathway was enriched in MM samples with highly expressed SPAG5 from GSE datasets. There was a concurrent downregulation of phosphorylation levels in the AKT/mTOR pathway. Yet OE of SPAG5 could restore the cell growth and p-AKT levels in MM cells after treatment with the AKT inhibitor MK2206. Taken together, SPAG5 could serve as a novel biomarker, and targeting the SPAG5 might have therapeutic potential in MM.

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出版当年[2021]版:
大类 | 4 区 医学
小类 | 4 区 肿瘤学 4 区 血液学
最新[2023]版:
大类 | 4 区 医学
小类 | 4 区 血液学 4 区 肿瘤学
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出版当年[2020]版:
Q3 HEMATOLOGY Q3 ONCOLOGY
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Q3 ONCOLOGY Q3 HEMATOLOGY

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第一作者机构: [1]Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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通讯机构: [1]Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China [2]Department of General Practice, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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