Aerobic glycolysis and tumor progression of hepatocellular carcinoma are mediated by ubiquitin of P53 K48-linked regulated by TRIM37

Ge, Yuzhen; Zhao, Rui; Li, Bo; Xiao, Benli; Zhou, Lei; Zuo, Shi

doi:10.1016/j.yexcr.2022.113377

Cited by 13 publications

(4 citation statements)

References 34 publications

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“…Furthermore, it has been demonstrated that p53 is a substrate of UBE2C; specifically, UBE2C facilitates p53 protein degradation in a ubiquitination-dependent manner in endometrial cancer cells [16] . Additionally, p53 has been reported to be involved in aerobic glycolysis in several types of cancers, such as hepatocellular carcinoma [ 40 , 41 ], breast cancer [ 42 , 43 ] and colon cancer [44] . Thus, we hypothesized that UBE2C may enhance TMZ resistance in glioma cells by downregulating p53 to trigger aerobic glycolysis.…”

Section: Discussionmentioning

confidence: 99%

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

Zhou,

Wang,

et al. 2024

ABBS

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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. TMZresistant 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.

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Section: Discussionmentioning

confidence: 99%

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

Zhou,

Wang,

et al. 2024

ABBS

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“…Further, the Nogo-B receptor was seen to promote the growth of human LIHC cells through the Akt signaling pathway ( 29 ), while inhibiting RFX6 inhibited the invasion ability of tumor cells through the Notch pathway and affected tumor immunity in LIHC ( 30 ). Finally, aerobic glycolysis and tumor progression in LIHC was seen to be mediated by P53 K48-linked ubiquitin regulated by TRIM37 ( 31 ). These research results are good references for our further in vivo and in vitro experiments of PLAU in LIHC.…”

Section: Discussionmentioning

confidence: 99%

Effect of urokinase-type plasminogen activator combined with clinical stage and Barcelona Clinic Liver Cancer stage on the prognosis of patients with hepatocellular carcinoma

Wu¹,

Sun²,

Li³

et al. 2023

J Gastrointest Oncol

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Background The aim of this investigation is to evaluate the association and potential mechanism between plasminogen activator urokinase (PLAU) and the prognosis of patients with liver hepatocellular carcinoma (LIHC). Methods We verified PLAU expression and its correlation with LIHC patients’ prognosis in The Cancer Genome Atlas (TCGA) database. The interaction network for protein-gene was established in the GeneMania database and the STRING database, and the association between PLAU and immune cells was assessed in Tumor Immune Estimation Resource (TIMER) and TCGA databases. The potential physiological mechanism was elucidated by the Gene Set Enrichment Analysis (GSEA) enrichment assessment. Finally, the individual clinical data of 100 LIHC patients were retrospectively evaluated to further analyze the clinical value of PLAU. Results The PLAU expression in LIHC tissues was greater than in paracancerous tissues, and LIHC patients with low PLAU expression had better disease-specific survival (DSS), overall survival (OS), and progression free interval (PFI) than those with high PLAU expression. In the TIMER database, the PLAU expression was positively associated with six kinds of infiltrating immune cells: CD4 + T, neutrophils, CD8 + T, macrophages, B, and dendritic cells, while GSEA enrichment analysis indicated PLAU may impact the biological activities of LIHC by taking part in MAPK and JAK_STAT signaling pathways, angiogenesis, and P53. There were statistically significant differences in T-stage and Edmondson grading between the two groups of patients with high and low expression of PLAU (P<0.05). The tumor progression rates were 88% (44/50) and 92% (46/50) respectively in the low and high PLAU groups, with early recurrence rates of 60% (30/50) and 72% (36/50), and median PFS of 29.5 and 23 months, respectively. The COX regression analysis showed PLAU expression and CS and Barcelona Clinic Liver Cancer (BCLC) stages were independent prognostic factors affecting tumor progression in LIHC patients. Conclusions The decreased expression of PLAU can prolong the DSS, OS, and PFI in LIHC patients, and can be utilized as a novel predictive index. PLAU combined with CS staging and BCLC staging has good clinical value in the early screening and prognosis of LIHC. These results reveal an efficient approach for developing anticancer strategies against LIHC.

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“…TRIM37 accentuates the malignant characteristics of HCC by liaising with the p53 protein, invoking E3 ligase activity, promoting ubiquitination, degradation, and favoring the glycolytic pathway. Neutralizing p53 effectively counters TRIM37’s promotive impact on HCC cell growth and metastasis ( 106 ). TRIM29 has connections to a diverse range of human malignancies.…”

Section: Trim Family and Mafldmentioning

confidence: 99%

The role of TRIM family in metabolic associated fatty liver disease

Zhang,

Ren

et al. 2023

Front. Endocrinol.

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Metabolic associated fatty liver disease (MAFLD) ranks among the most prevalent chronic liver conditions globally. At present, the mechanism of MAFLD has not been fully elucidated. Tripartite motif (TRIM) protein is a kind of protein with E3 ubiquitin ligase activity, which participates in highly diversified cell activities and processes. It not only plays an important role in innate immunity, but also participates in liver steatosis, insulin resistance and other processes. In this review, we focused on the role of TRIM family in metabolic associated fatty liver disease. We also introduced the structure and functions of TRIM proteins. We summarized the TRIM family’s regulation involved in the occurrence and development of metabolic associated fatty liver disease, as well as insulin resistance. We deeply discussed the potential of TRIM proteins as targets for the treatment of metabolic associated fatty liver disease.

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Aerobic glycolysis and tumor progression of hepatocellular carcinoma are mediated by ubiquitin of P53 K48-linked regulated by TRIM37

Cited by 13 publications

References 34 publications

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

Effect of urokinase-type plasminogen activator combined with clinical stage and Barcelona Clinic Liver Cancer stage on the prognosis of patients with hepatocellular carcinoma

The role of TRIM family in metabolic associated fatty liver disease

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