title: Ubiquitin-specific protease 28 is overexpressed in human glioblastomas and contributes to glioma tumorigenicity by regulating MYC expression.
abstract: The transcription factor MYC, which is dysregulated in the majority of gliomas, is difficult to target directly. Deubiquitinase ubiquitin-specific protease 28 (USP28) stabilizes oncogenic factors, including MYC. However, the contribution of USP28 in tumorigenesis, particularly in glioma, is unknown. Here, we determined the expression of USP28 and assessed its clinical significance in human glioma. We found that USP28 is overexpressed in human glioma but not in normal brain tissue. The level of USP28 protein expression in human glioma tissues was directly correlated with glioma grade. Meanwhile, the level of USP28 protein expression in human glioblastoma tissues was inversely correlated with patient survival. Enforced USP28 expression promotes SW1783 glioma cell proliferation. Moreover, gliomas that arose from USP28-transfected SW1783 cells displayed tumorigenicity in nude mouse model systems. Inhibition of USP28 expression in glioblastoma U373 cells suppressed anchorage-independent growth in vitro and tumorigenicity in vivo. Furthermore, USP28 regulates the expression of MYC protein, which is essential in USP28-induced cell growth in glioma cells. These results showed that USP28 is overexpressed in human glioblastomas and it contributes to glioma tumorigenicity. Therefore, USP28 could be a new target of therapy for human malignant glioma.
authors.affiliation: Department of Neurosurgery, Weifang People's Hospital, Weifang 261041, Shandong, China.
authors.forename: Zengwu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Linyi People's Hospital, Linyi, 276000, Shandong, China.
authors.forename: Qimin
authors.initials: Q
authors.lastname: Song
authors.affiliation: Department of Neurosurgery, Jining No.1 People's Hospital, Jining 272002, Shandong, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xue
authors.affiliation: Department of Neurosurgery, Linyi People's Hospital, Linyi, 276000, Shandong, China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, Weifang People's Hospital, Weifang 261041, Shandong, China shiqiangqindoc@163.com.
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Qin
mesh_terms: D000328:Adult; D000818:Animals; D015197:Carcinogenicity Tests; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D005910:Glioma / Q000473:pathology*; D006801:Humans; D008819:Mice, Nude; D016513:Mice, SCID; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis*; D016019:Survival Analysis; D043222:Ubiquitin Thiolesterase / Q000032:analysis*
chemical_list: D016271:Proto-Oncogene Proteins c-myc; C442902:USP28 protein, human; D043222:Ubiquitin Thiolesterase
keywords: MYC; Ubiquitin-specific protease 28; glioma