title: Carboxyl terminus of Hsp70-interacting protein (CHIP) contributes to human glioma oncogenesis.
abstract: Malignant glioma is the most common adult primary brain tumor, and the mechanism of its oncogenesis is poorly understood. Growing evidence has shown that E3 ubiquitin ligases can promote tumorgenesis of glioma. CHIP is an E3 ubiquitin ligase that can induce ubiquitylation and degradation of many tumor-related proteins, and it has been reported to act as an upstream regulator in breast cancer; however, its role in human gliomas has not been evaluated yet. In this study, the expression of CHIP in glioma tissues was studied using immunohistochemistry. CHIP expression in glioma cells was studied by real-time RT-PCR, western blot and double immunofluorescence staining. The role of CHIP in glioma oncogenesis was investigated by lentivirus-mediated RNA interference (RNAi) and overexpression in vitro and in vivo. We showed CHIP expression in glioma samples was related to tumor grades, with stronger staining in high-grade gliomas than in low-grade gliomas. Knocking down of CHIP suppressed proliferation, colony formation of U251 and U87 glioma cells, while overexpression of CHIP resulted in enhanced proliferation and colony formation in vitro. In a nude mouse xenograft model, intratumoral injection of CHIP RNAi lentivirus significantly delayed tumor growth. In contrast, overexpression of CHIP resulted in enhanced tumor growth in vivo. After CHIP RNAi, both survivin mRNA and protein were decreased, while CHIP overexpression induced increased mRNA and protein levels of survivin. This is the first study demonstrating CHIP contributes to oncogenesis of glioma.
authors.affiliation: Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhou
authors.forename: Jingxu
authors.initials: J
authors.lastname: Zhou
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Yong
authors.initials: Y
authors.lastname: Yan
authors.forename: Weiqing
authors.initials: W
authors.lastname: Li
authors.forename: Chunlin
authors.initials: C
authors.lastname: Wang
authors.forename: Guohan
authors.initials: G
authors.lastname: Hu
authors.forename: Yicheng
authors.initials: Y
authors.lastname: Lu
authors.forename: Juxiang
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000077022:Survivin; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin; C467728:STUB1 protein, human; D044767:Ubiquitin-Protein Ligases