Glutathione S-Transferase Omega 1 Regulates Vimentin Expression Based on Active Site and Promote Malignancy of Lung Adenocarcinoma
Objective:To investigate the relationship between key activity site Cys32 of Glutathione S-Transferase Omega 1(GSTO1)and malignant progression of lung adenocarcinoma,and to clarify the potential mechanism.Methods:Wild-type(GSTO1WT)and inactivation mutant GSTO1(GSTO1C32A)were overexpressed in lung adenocarcinoma PC9 cells by lentivirus packaging and infection system.Western blot assay was used to verify whether the model was constructed successfully.Cell morphology was investigated by inverted phase-contrast microscopy.CCK8 assay and clonogenic assay were performed to detect cell proliferation.Clinical data mining was used to explore the cancer-promoting protein regulated by GSTO1,and western blot assay was performed to verify protein levels in GSTO1WT and GSTO1C32A overexpressed lung adenocarcinoma cell lines.Correlation between expression levels and clinical stage,differentiation,metastasis,and survival of lung adenocarcinoma patients using clinical databases.Results:Morphological changes of lung adenocarcinoma cells was induced by GSTO1WT instead of GSTO1C32A overexpression.Comparing with GSTO1C32A overexpression and empty vehicle group,GSTO1WT overexpression promoted the proliferation of PC9 cells.Clinical data suggested that there was a positive correlation between the expression of GSTO1 and vimentin(VIM),and western blot assay showed that the overexpression of GSTO1WT upregulated protein level of vimentin,while GSTO1C32A overexpression not.Clinical data mining showed that lung adenocarcinoma patients with high co-expression of GSTO1 and vimentin were associated with a greater degree of tumor malignancy and a higher proportion of metastasis,as well as shorter disease-free survival and overall survival.Conclusion:The GSTO1 regulates expression of vimentin based on its enzyme-active site and promote the malignancy of lung adenocarcinoma,which indicates that GSTO1 was a potential metabolic vulnerability in lung adenocarcinoma.
NETL
NSTL
万方数据
维普
