UCHL5 inhibits U251 glioma cell proliferation and tumor growth via stabilizing and deubiquitinating PTEN  

作　　者：YUE XIAO WENJING MA XINYI CHEN WEIWEI HU QIANQIAN DI XIBAO ZHAO GUODONG HUANG WEILIN CHEN 

机构地区：[1]Guangdong Provincial Key Laboratory of Regional Immunity and Diseases,Department of Neurosurgery,Shenzhen Second People’s Hospital,The first Affiliated Hospital of Shenzhen University,Shenzhen University Medical School,Shenzhen University,Shenzhen,518055,China [2]Institute of Biological Therapy,Department of Immunology,Shenzhen University,Shenzhen,518055,China [3]Department of Neurosurgery,Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,310058,China

出　　处：《BIOCELL》2023年第12期2617-2625,共9页生物细胞（英文）

基　　金：supported by grants from the Shenzhen Science and Technology Innovation Commission Grant(Nos.JCYJ20180507182253653 and JCYJ20190808172201639);Guangdong Province Basic and Applied Basic Research Fund(No.2022A1515111143).

摘　　要：Glioma is the most common primary brain tumor.Exploration of new tumorigenesis mechanism of glioma is critical to determine more effective treatment targets as well as to develop effective prognosis methods that can enhance the treatment efficacy.We previously demonstrated that the deubiquitinase biquitin carboxyl-terminal hydrolase L5(UCHL5)was downregulated in human glioma.However,the effect and mechanism of UCHL5 on the proliferation of glioma cells remains unknown.Methods:Transfection of siRNA was used to knockdown the expression of UCHL5 in U251 cells.The 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide(MTT)assay,Edu assay,and colony formation assay were employed to identify the effect of UCHL5 on the proliferation of U251 glioma cells.Western blotting and quantitative real-time PCR were carried out to detect the interaction of UCHL5 and PTEN.The effect of UCHL5 on the growth of glioma in vivo was evaluated in nude mice.Then Immunohistochemistry(IHC)were performed to analysis the expression of UCHL5 and PTEN in human glioma tissues.Results:Here,we have reported that silencing of UCHL5 could promote the proliferation of U251 glioma cells through MTT assay,Edu assay,and colony formation assay.Mechanically,we revealed that UCHL5 stabilizes the phosphatase and tensin homolog(PTEN)expression by deubiquitination,thereby inhibiting cell proliferation in U251 cells.Tumor xenograft experiments further demonstrated that silencing the UCHL5 expression could accelerate U251 cell growth in vivo.Finally,in human glioma tissue microarray,the positive correlation between UCHL5 and PTEN expression was confirmed through IHC assay.Conclusion:UCHL5 restrains the proliferation of U251 glioma cells by stabilizing and deubiquitinating PTEN.Our findings provide ideas for developing enhanced targeted PTEN therapy for patients with glioma.

关 键 词：UBIQUITINATION GLIOBLASTOMA TUMORIGENESIS UCH37 

分 类 号：R739.41[医药卫生—肿瘤]