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NRF‑1 directly regulates TFE3 and promotes the proliferation of renal cancer cells

  • Authors:
    • Wenyuan Zhuang
    • Xiang Dong
    • Bo Wang
    • Ning Liu
    • Hongqian Guo
    • Chunni Zhang
    • Weidong Gan
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing University, Nanjing, Jiangsu 210008, P.R. China, Department of Urology, Drum Tower Clinical Medical School of Nanjing Medical University, Nanjing University, Nanjing, Jiangsu 210008, P.R. China, Department of Clinical Laboratory, Jinling Hospital, Nanjing University School of Medicine, Nanjing University, Nanjing, Jiangsu 210008, P.R. China
    Copyright: © Zhuang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 679
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    Published online on: July 22, 2021
       https://doi.org/10.3892/ol.2021.12940
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Abstract

The role of transcription factor binding to IGHM enhancer 3 (TFE3) in renal cell carcinoma (RCC) is not well understood. Nuclear respiratory factor 1 (NRF‑1) may be the positive upstream regulatory gene of TFE3. The aim of the present study was to determine whether NRF‑1 could directly regulate the expression of TFE3 and regulate tumorigenesis and progression of RCC through TFE3. Short hairpin RNA (shRNA) was used to silence the expression of NRF‑1 in the 786‑O human kidney adenocarcinoma cell line and the 293T human embryonic kidney cell line. Luciferase reporter assays were used to determine the relationship between NRF‑1 and TFE3. The CHIP experiment was used to verify the actual binding of NRF‑1 and TFE3 promoter regions. MitoTimer staining was used to measure mitochondrial biosynthesis. Flow cytometry was used to detect cell cycle and apoptosis. The 786‑O and 293T cells were used to examine the underlying mechanism of action. The results demonstrated that NRF‑1 could bind to the promoter region of the TFE3 gene and directly regulate the expression of TFE3. Following NRF‑1 knockdown, the protein levels of phosphorylated (p)‑AKT and p‑S6 of mTOR pathway was inhibited, cell cycle progression was blocked, the levels of apoptosis increased, and mitochondrial generation was reduced. Following overexpression of TFE3, the levels of mTOR‑associated markers were restored in NRF‑1 knockdown cells. These findings suggest that NRF‑1 may regulate the mTOR pathway through TFE3 and regulate the energy metabolism, proliferation and growth of cancer cells by directly regulating the expression of TFE3.
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Copy and paste a formatted citation
Spandidos Publications style
Zhuang W, Dong X, Wang B, Liu N, Guo H, Zhang C and Gan W: NRF‑1 directly regulates TFE3 and promotes the proliferation of renal cancer cells. Oncol Lett 22: 679, 2021.
APA
Zhuang, W., Dong, X., Wang, B., Liu, N., Guo, H., Zhang, C., & Gan, W. (2021). NRF‑1 directly regulates TFE3 and promotes the proliferation of renal cancer cells. Oncology Letters, 22, 679. https://doi.org/10.3892/ol.2021.12940
MLA
Zhuang, W., Dong, X., Wang, B., Liu, N., Guo, H., Zhang, C., Gan, W."NRF‑1 directly regulates TFE3 and promotes the proliferation of renal cancer cells". Oncology Letters 22.3 (2021): 679.
Chicago
Zhuang, W., Dong, X., Wang, B., Liu, N., Guo, H., Zhang, C., Gan, W."NRF‑1 directly regulates TFE3 and promotes the proliferation of renal cancer cells". Oncology Letters 22, no. 3 (2021): 679. https://doi.org/10.3892/ol.2021.12940
Copy and paste a formatted citation
x
Spandidos Publications style
Zhuang W, Dong X, Wang B, Liu N, Guo H, Zhang C and Gan W: NRF‑1 directly regulates TFE3 and promotes the proliferation of renal cancer cells. Oncol Lett 22: 679, 2021.
APA
Zhuang, W., Dong, X., Wang, B., Liu, N., Guo, H., Zhang, C., & Gan, W. (2021). NRF‑1 directly regulates TFE3 and promotes the proliferation of renal cancer cells. Oncology Letters, 22, 679. https://doi.org/10.3892/ol.2021.12940
MLA
Zhuang, W., Dong, X., Wang, B., Liu, N., Guo, H., Zhang, C., Gan, W."NRF‑1 directly regulates TFE3 and promotes the proliferation of renal cancer cells". Oncology Letters 22.3 (2021): 679.
Chicago
Zhuang, W., Dong, X., Wang, B., Liu, N., Guo, H., Zhang, C., Gan, W."NRF‑1 directly regulates TFE3 and promotes the proliferation of renal cancer cells". Oncology Letters 22, no. 3 (2021): 679. https://doi.org/10.3892/ol.2021.12940
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