title: Ubiquitin-protein ligase E3C promotes glioma progression by mediating the ubiquitination and degrading of Annexin A7.
abstract: The ubiquitin-protein ligase E3C (UBE3C) belongs to the E3 ligase enzyme family and implicates in the ubiquitin-proteasome pathway, thus regulates physiological and cancer-related processes. Here, we investigated the expression and roles of UBE3C in glioma. We demonstrated that UBE3C was overexpressed in glioma tissues and cell lines. Inhibition of UBE3C expression in glioma cells significantly decreased cell migration and invasion in vitro. Mechanistically, we disclosed that UBE3C physically interacted with and ubiquitinated tumor suppressor gene annexin A7 (ANXA7), resulting in ubiquitination and degradation of ANXA7. Our results also revealed that increased UBE3C expression was accompanied by a reduction in ANXA7 protein expression in glioma tissues, but not ANXA7 mRNA. Importantly, the inhibition of ANXA7 expression in gliomas cells with UBE3C interference could rescue the cell invasion. Clinically, UBE3C overexpression significantly correlated with high-grade tumors (p < 0.05), poor overall survival, and early tumor recurrence. Thus, our data reveal that high UBE3C expression contributes to glioma progression by ubiquitination and degradation of ANXA7, and thus presents a novel and promising target for glioma therapy.
authors.affiliation: Department of Neurosurgery, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, P.R. China.
authors.forename: Si-Jian
authors.initials: SJ
authors.lastname: Pan
authors.affiliation: Department of Stereotactic and Functional Neurosurgery, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, P.R. China.
authors.forename: Shi-Kun
authors.initials: SK
authors.lastname: Zhan
authors.affiliation: Department of Neurology, Qinghai Provincial People's Hospital, Xining, 810007, P.R. China.
authors.forename: Wei-Zhong
authors.initials: WZ
authors.lastname: Ji
authors.affiliation: Department of Stereotactic and Functional Neurosurgery, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, P.R. China.
authors.forename: Yi-Xin
authors.initials: YX
authors.lastname: Pan
authors.affiliation: Department of Stereotactic and Functional Neurosurgery, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Stereotactic and Functional Neurosurgery, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, P.R. China.
authors.forename: Dian-You
authors.initials: DY
authors.lastname: Li
authors.affiliation: Department of Stereotactic and Functional Neurosurgery, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.affiliation: Department of Stereotactic and Functional Neurosurgery, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, P.R. China.
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Zhang
authors.affiliation: Department of Stereotactic and Functional Neurosurgery, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, P.R. China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Cao
authors.affiliation: Department of Stereotactic and Functional Neurosurgery, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, P.R. China.
authors.forename: Liu-Guan
authors.initials: LG
authors.lastname: Bian
authors.affiliation: Department of Stereotactic and Functional Neurosurgery, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, P.R. China.
authors.forename: Bomin
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Neurosurgery, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, 200025, P.R. China.
authors.forename: Qing-Fang
authors.initials: QF
authors.lastname: Sun
mesh_terms: D017310:Annexin A7 / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D059748:Proteolysis; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis* / Q000235:genetics; D054875:Ubiquitination
chemical_list: D017310:Annexin A7; D025521:Tumor Suppressor Proteins; C555759:UBE3C protein, human; D044767:Ubiquitin-Protein Ligases