Open Access

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

  • Published online on: July 22, 2021     https://doi.org/10.3892/ol.2021.12940
  • Article Number: 679
  • Copyright: © Zhuang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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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September-2021
Volume 22 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Copy and paste a formatted citation
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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