|Table of Contents|

TRIM2 regulates glycolysis in hepatocellular carcinoma cells through ubiquitination modification of PKM2

Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:
2023 20
Page:
3743-3750
Research Field:
Publishing date:

Info

Title:
TRIM2 regulates glycolysis in hepatocellular carcinoma cells through ubiquitination modification of PKM2
Author(s):
TANG Jintian1; TANG Runjuan2; XUE Feng1; YI Chao1; LI Wanghong1; LIU Chen1
1.Department of Hepatobiliary and Pancreatic Surgery,Cancer Hospital Affiliated to Xinjiang Medical University,Xinjiang Urumqi 830000,China;2.Department of Rehabilitation,the Second Affiliated Hospital of Xinjiang Medical University,Xinjiang Urumqi 830000,China.
Keywords:
hepatocellular carcinoma; TRIM2; PKM2; ubiquitination; glycolysis
PACS:
R735.7
DOI:
10.3969/j.issn.1672-4992.2023.20.005
Abstract:
Objective:To explore the mechanism of TRIM2 regulating glycolysis in hepatocellular carcinoma cells through ubiquitination modification of PKM2.Methods:The TCGA and CPTAC databases were analyzed for TRIM2 gene and protein expression levels and correlated with patient survival status.HepG2-shNC and HepG2-shTRIM2 cell lines were constructed,and cellular energy metabolism meter was used to detect the extracellular acidification rate and oxygen consumption rate of both groups of cells,and to measure cellular glucose consumption rate,lactate production and ATP levels.Immunoprecipitation verified the interaction between TRIM2 and PKM2 in HepG2 and HEK293T cells,and immunofluorescence detected the co-localization of PKM2 and TRIM2.Ubiquitination modification of PKM2 after knockdown/over-expression of TRIM2 in HepG2/HEK293T cells was detected by immunoprecipitation,and the PKM2 enzymatic activity after knockdown/over-expression of TRIM2 in HepG2/HEK293T cells was detected by enzyme catalyzed reaction in vitro.Transwell assay was performed to detect the invasion and migration ability of HepG2-shNC and HepG2-shTRIM2 cells.Xenograft models were performed to evaluate the tumorigenic ability of HepG2-shNC and HepG2-shTRIM2 cells in vivo.Results:The analysis of TCGA and CPTAC databases revealed that TRIM2 expression levels were elevated at mRNA and protein expression in hepatocellular carcinoma tissues,and high TRIM2 expression predicted poor patient survival.TRIM2 expression levels correlated highly with the glycolytic pathway,and knockdown of TRIM2 inhibited HepG2 extracellular acidification rate,increased oxygen consumption rate,otherwise cellular glucose consumption rate［(100.000 0±2.000 0)% vs (46.666 7±8.144 5)%］,lactate production［(99.000 0±3.605 5)% vs (43.666 7±10.016 65)%］,and ATP levels［(97.000 0±3.605 5)% vs (57.333 3±6.658 3)%］ were significantly down-regulated.TRIM2 interacted with PKM2 directly in HepG2 cells and the co-localization of PKM2 and TRIM2 was detected.PKM2 ubiquitination levels were improved and PKM2 enzyme activity was decreased in HepG2 cells after TRIM2 inhibition.Myc-TRIM2 expressed in HEK293T cells.The level of PKM2 protein ubiquitination modifications down-regulated and PKM2 enzyme activity increased.Knockdown of TRIM2 inhibited HepG2 cell invasion ability (1 vs 0.506 7±0.116 8),migration ability (1 vs 0.513 3±0.0862 2),tumorigenic volume［(529.333 3±29.280 26)mm3 vs (281.666 7±25.696 9)mm3］ and weight［(360.333 3±42.716 1)mg vs (172.166 7±50.284 9)mg］ of cells in vivo.Conclusion:TRIM2 is highly expressed in hepatocellular carcinoma tissues,and PKM2 enzymatic activity is promoted by deubiquitinating modification by TRIM2,thereby regulating the glycolytic capacity of tumor cells.

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Memo

Memo:
新疆维吾尔自治区自然科学基金项目（编号：2021D01C399）
Last Update: 1900-01-01