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Effect of glutathione reductase knockdown in response to UVB-induced oxidative stress in human lung adenocarcinoma.

ABSTRACT: BACKGROUND:Glutathione reductase (GR) plays a critical role in the maintenance of physiological redox status in cells. However, the comprehensive investigations of GR-modulated oxidative stress have not been reported. METHODS:In the present study, we cultured a human lung adenocarcinoma line CL1-0 and its GR-knockdown derivative CL1-0?GR to evaluate their differential responses to UVB-irradiation. RESULTS:We identified 18 proteins that showed significant changes under UVB-irradiation in CL1-0?GR cells rather than in CL1-0 cells. Several proteins involving protein folding, metabolism, protein biosynthesis and redox regulation showed significant changes in expression. CONCLUSIONS:In summary, the current study used a comprehensive lung adenocarcinoma-based proteomic approach for the identification of GR-modulated protein expression in response to UVB-irradiation. To our knowledge, this is the first global proteomic analysis to investigate the role of GR under UVB-irradiation in mammalian cell model.

SUBMITTER: Chou HC

PROVIDER: S-EPMC3905656 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Effect of glutathione reductase knockdown in response to UVB-induced oxidative stress in human lung adenocarcinoma.

Chou Hsiu-Chuan HC Chan Hong-Lin HL

Proteome science 20140109 1

<h4>Background</h4>Glutathione reductase (GR) plays a critical role in the maintenance of physiological redox status in cells. However, the comprehensive investigations of GR-modulated oxidative stress have not been reported.<h4>Methods</h4>In the present study, we cultured a human lung adenocarcinoma line CL1-0 and its GR-knockdown derivative CL1-0ΔGR to evaluate their differential responses to UVB-irradiation.<h4>Results</h4>We identified 18 proteins that showed significant changes under UVB-i ...[more]

PMID: 24405781

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Project description:Background: Oxidative stress (OxS) participates in a variety of biological processes, and is considered to be related to the occurrence and progression of many tumors; however, the potential diagnostic value of OxS in lung cancer remains unclear. Methods: The clinicopathological and transcriptome data for lung adenocarcinoma (LUAD) were collected from TCGA and GEO database. LASSO regression was used to construct a prognostic risk model. The prognostic significance of the OxS-related genes was explored using a Kaplan-Meier plotter database. The prediction performance of the risk model was shown in both the TCGA and GSE68465 cohorts. The qRT-PCR was performed to explore the expression of genes. CCK-8, Edu and transwell assays were conducted to analyze the role of CAT on cell proliferation migration and invasion in lung cancer. Immune infiltration was evaluated by CIBERSORT and mutational landscape was displayed in the TCGA database. Moreover, the relationship between risk score with drug sensitivity was investigated by pRRophetic. Results: We identified a prognosis related risk model based on a four OxS gene signature in LUAD, including CYP2D6, FM O 3, CAT, and GAPDH. The survival analysis and ROC curve indicated good predictive power of the model in both the TCGA and GEO cohorts. LUAD patients in the high-risk group had a shorter OS compared to the low-risk group. QRT-PCR result showed that the expression of four genes was consistent with previous analysis in cell lines. Moreover, overexpression of CAT could decrease the proliferation, invasion and migration of lung cancer cells. The Cox regression analysis showed that the risk score could be used as an independent prognostic factor for OS. LUAD patients in the high-risk score group exhibited a higher tumor mutation burden and risk score were closely related to tumor associated immune cell infiltration, as well as the expression of immune checkpoint molecules. Both the high- and low-risk groups have significant differences in sensitivity to some common chemotherapy drugs, such as Paclitaxel, Docetaxel, and Vinblastine, which may contribute to clinical treatment decisions. Conclusion: We established a robust OxS-related prognostic model, which may contribute to individualized immunotherapeutic strategies in LUAD.

Dataset Information

Effect of glutathione reductase knockdown in response to UVB-induced oxidative stress in human lung adenocarcinoma.

Publications

Effect of glutathione reductase knockdown in response to UVB-induced oxidative stress in human lung adenocarcinoma.

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