UBE2C enhances temozolomide resistance by regulating the expression of p53 to induce aerobic glycolysis in glioma.

Abstract

UBE2C is overexpressed in gliomas, and its overexpression has been reported to be correlated with the drug resistance of gliomas to some extent. In this study, we explore the role of UBE2C in regulating temozolomide (TMZ) resistance in glioma and investigate the underlying mechanisms involved. Twenty normal brain tissues and 100 glioma tissues from 50 TMZ-resistant patients and 50 TMZ-sensitive patients are included in this study. TMZ-resistant cell lines are constructed to explore the role of UBE2C in regulating glioma cell viability and TMZ resistance. Our results show that both the mRNA and protein levels of UBE2C are significantly elevated in the brain tissues of glioma patients, especially in those of TMZ-resistant patients. Consistently, UBE2C expression is markedly upregulated in TMZ-resistant cell lines. Overexpression of UBE2C rescues glioma cells from TMZ-mediated apoptosis and enhances cell viability. In contrast, downregulation of UBE2C expression further enhances TMZ function, increases cell apoptosis and decreases cell viability. Mechanistically, UBE2C overexpression decreases p53 expression and enhances aerobic glycolysis level by increasing ATP level, lactate production, and glucose uptake. Downregulation of p53 level abolishes the role of UBE2C downregulation in inhibiting TMZ resistance and aerobic glycolysis in glioma cells. Moreover, an animal assay confirms that downregulation of UBE2C expression further suppresses tumor growth in the context of TMZ treatment. Collectively, this study reveals that downregulation of UBE2C expression enhances the sensitivity of glioma cells to TMZ by regulating the expression of p53 to inhibit aerobic glycolysis.

• Authors: Kun Zhou, Dexin Wang, Xiaolin Du, Xia Feng, Xiaoxi Zhu, Cheng Wang
• Journal: Acta biochimica et biophysica Sinica (Acta Biochim Biophys Sin (Shanghai)) (Apr 18 2024) ISSN: 1745-7270 [Electronic] China
• PMID: 38634120 (Publication Type: Journal Article)