F-Box Protein 11 Suppresses Cell Proliferation and Aerobic Glycolysis in Glioblastomas by Mediating the Ubiquitin Degradation of Cdc25A. Issue 7 (18th May 2022)

• Record Type: Journal Article
• Authors: Liu, Chao; Chen, Xi; Zhang, Li; Liu, Jiaxiu; Li, Chunmei; Zhao, Jinxi; Pu, Jun; Tang, Peipei; Liu, Bolin; Huang, Xiaobin
• Is Part Of: Journal of neuropathology and experimental neurology. Volume 81:Issue 7(2022)
• Page Start: 511
• Page End: 521
• Publication Date: 2022-05-18
• Subjects: Aerobic glycolysis -- Cdc25A -- F-box protein 11 -- Glioblastoma -- Proliferation -- Ubiquitination; Neurology -- Diseases -- Periodicals; Neurology -- Diseases -- Physiopathology -- Periodicals; 616.8047
• DOI: 10.1093/jnen/nlac033
• Languages: English
• ISSNs: 0022-3069

Abstract

Abstract: Glioblastoma is a malignant CNS tumor with an extremely poor prognosis. F-box protein 11 (FBXO11) has E3 ubiquitin ligase activity and participates in the pathogenesis of multiple tumors but the role and mechanism of FBXO11 activity in glioblastoma remain unknown. In this study, FBXO11 was first observed to be downregulated in glioblastoma tissues and cell lines. 3-(4, 5)-dimethylthiahiazo (-z-y1)-3, 5-di- phenytetrazoliumromide (MTT) and colony formation assays and enzyme linked immunosorbent assay (ELISA) demonstrated that overexpression of FBXO11 suppressed proliferation and aerobic glycolysis and induced cell cycle arrest in U251-MG and A172 cells. FBXO1 decreased cell division cycle 25 A (Cdc25A) expression through ubiquitin degradation in a coprecipitation assay. A Western blot assay validated FBXO11 suppression of PKM2 dephosphorylation and c-Myc-mediated aerobic glycolysis via reduction of Cdc25A. In addition, a rescue experiment revealed that FBXO11 suppressed proliferation and aerobic glycolysis, both of which were reversed by overexpression of Cdc25A. FBXO11 overexpression also inhibited tumorigenesis via suppressing Cdc25A expression in vivo. These findings indicate that FBXO11 suppresses cell proliferation and aerobic glycolysis in glioblastomas by mediating the ubiquitin degradation of Cdc25A thereby providing insight into mechanisms of glioblastoma tumorigenesis and identifying a new potential therapeutic strategy.