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. 2021 Jul;10(2):327-333.
doi: 10.52547/rbmb.10.2.327.

Association Between NOX4 And Nrf2 Genes in Non-Small-Cell Lung Carcinoma: A Case-Control Study

Nasim Bakhtiyari  1 , Akbar Sharifi  1 , Younes Aftabi  1 , Neda Gilani  2 , Venus Zafari  1 , Atefeh Ansarin  1 , Ensiyeh Seyedrezazadeh  1
Affiliations

Association Between NOX4 And Nrf2 Genes in Non-Small-Cell Lung Carcinoma: A Case-Control Study

Nasim Bakhtiyari et al. Rep Biochem Mol Biol. 2021 Jul.

Abstract

Background: Epithelial malignancy in lung cancer, which is initiated with myofibroblast differentiation and remodeling, promotes hypoxia and intracellular ROS generation most affected by the prototypical enzyme, NADPH oxidase 4 (NOX4). In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) acts as a critical transcription factor by stimulating antioxidant proteins as redox homeostasis regulators. The aim of this study was to investigate a possible correlation between lung tissue NOX4 and Nrf2 genes (NOX4 and Nrf2) mRNA expression and bronchoalveolar lavage fluid (BALF) protein expression in non-small-cell lung carcinoma (NSCLC) patients.

Methods: Samples from 25 patients with various NSCLC types and stages and 20 healthy controls were collected. NOX4 and Nrf2 mRNA were measured by qRT-PCR, and protein by western blot analysis.

Results: NOX4 mRNA and protein expression was significantly up-regulated in NSCLC patients' lung tissues and BALFs (p= 0.03 and 0.01, respectively). In addition, by adjusting for age, sex, and NSCLC types and stages, a significant and positive correlation was observed between NOX4 and Nrf2 mRNA expression (r= 0.927, p= 0.001). This was also true when not adjusted as above (r= 0.944, p< 0.001).

Conclusion: NOX4 mRNA and protein expression is significantly up-regulated in NSCLC patients' lung tissues and BALFs, and NOX4 and Nrf2 mRNA expression is positively correlated in NSCLC tissues.

Keywords: Gene expression; NOX4; Non-small-cell lung cancer; Nrf2.

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Figures

Fig. 1
Fig. 1
Nrf2 and NOX4 expression in tissue samples and abundance of their associated proteins in the BALFs by RT-PCR and western blotting. (a) Nrf2 and NOX4 expression in the NSCLC patient tissue samples was greater than in controls, however, the increase was statistically significant only for NOX4 (p= 0.03). (b) The protein levels, by western blotting. (c) Densitometry revealed greater abundances of both Nrf2 and NOX4 protein in patient BALFs than in controls, however as with the mRNAs, the difference was significant only for NOX4 (p= 0.01).
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