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

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

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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 re-sistance.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 mark-edly 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 down-regulation of UBE2C expression enhances the sensitivity of glioma cells to TMZ by regulating the expression of p53 to inhibit aerobic glycolysis.

UBE2Cp53TMZ resistanceaerobic glycolysisglioma

Kun Zhou、Dexin Wang、Xiaolin Du、Xia Feng、Xiaoxi Zhu、Cheng Wang

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Department of Neurosurgery,the Jinyang Hospital Affiliated to Guizhou Medical University,Guiyang 550084,China

Department of Sleep Medicine,the Second People's Hospital of Guizhou Province,Guiyang 550084,China

Key Laboratory of Cell Engineering of Guizhou Province,Affiliated Hospital of Zunyi Medical University,Zunyi 563000,China

Science and Technology Foundation of Guizhou Provincial Health and Family Planning CommissionScience and Technology Foundation of Guizhou Provincial Health and Family Planning CommissionScience and Technology Foundation of Guizhou Provincial Health and Family Planning CommissionPostgraduate Research Foundation of Guizhou ProvinceGuizhou Province Science and Technology Planning ProjectGuizhou Provincial Health Commission

gzwjkj2019-1-145gzwkj2023-036Gzwjkj2017-1-026QIAN JIAO HE YJSKYJJ[2021]206GuizhouGeneticBasis-ZK[2023]General326gzwkj2023-036

2024

10.3724/abbs.2024033

生物化学与生物物理学报(英文版)
中国科学院上海生物化学研究所

生物化学与生物物理学报(英文版)

CSTPCD
影响因子：0.772
ISSN：1672-9145
年,卷(期)：2024.56(6)
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