Transcription factor NRF2 and the expression of the Hippo pathway effector TAZ in bladder tumorigenesis are significantly correlated

转录因子NRF2与Hippo通路效应因子TAZ的表达在膀胱肿瘤发生中具有显著相关性。

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Abstract

Bladder cancer ranks as the 11th most frequent form of cancer and is the most common malignancy of urinary tract cells. A major contributor to bladder cancer development is oxidative stress. The nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that regulates the expression of the transcriptional coactivator with PDZ-binding motif (TAZ) and is found to regulate oxidative stress in cancer cells. This study aimed to investigate the relationship between oxidative stress and the NRF2/TAZ pathway in bladder cancer. In this study, a total of 35 bladder cancer patients and 35 healthy subjects were recruited. The expression of NRF2 and TAZ genes was evaluated using real-time PCR. Total Oxidant Status (TOS) and total antioxidant capacity (TAC) of the samples were measured. Our findings revealed a higher expression of NRF2 (p < 0.001) and TAZ (p < 0.001) mRNA in cancerous tissue as compared to healthy subjects. We also found that there is a positive correlation between tumor grading and NRF2 (r = 0.522, p = 0.001) as well as TAZ (r = 0.462, p = 0.02) genes mRNA expression. Also, our results revealed that there is a significant correlation between TAZ and NRF2 genes mRNA expression in bladder cancer patients. Furthermore TAC level was considerably lower in bladder cancer patients (p < 0.01), while the TOS level was significantly higher compared to the control group(p < 0.05). Finally, our findings suggested that NRF2 and TAZ, as transcriptional factors, are associated with higher grades of bladder cancer as well as oxidative stress in patients with bladder cancer.

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