Open Access

Inhibition of SND1 overcomes chemoresistance in bladder cancer cells by promoting ferroptosis

  • Authors:
    • Yu Zhao
    • Pengpeng Ren
    • Zhiqin Yang
    • Lei Wang
    • Changhua Hu
  • View Affiliations

  • Published online on: November 25, 2022     https://doi.org/10.3892/or.2022.8453
  • Article Number: 16
  • Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Chemotherapy remains one of the most important adjuvant treatments for bladder cancer (BC). However, similar to other malignancies, BC is prone to chemotherapy resistance and only approximately half of muscle‑invasive patients with BC respond to chemotherapy. The present study aimed to reveal the mechanisms underlying chemoresistance in BC cells. Cell viabilities were assessed by CCK‑8 assay. The differentiated expression of genes in chemoresistant and their parental BC cells were examined by RNA sequencing. Cell death was determined by flow cytometry. Different cell death inhibitors were used to determine the types of cell death. Levels of reactive oxygen species, iron, glutathione and malondialdehyde were assessed using the corresponding commercial kits. ChIP and dual luciferase activity assays were performed to investigate the interaction between staphylococcal nuclease and tumour domain containing 1 (SND1) and glutathione peroxidase 4 (GPX4) mRNA. RNAi was used to knockdown SND1 or GPX4. The results revealed that SND1 in BC cells were insensitive to cisplatin, and inhibition of SND1 overcame this resistance. Silencing of SND1 enhanced cell death induced by cisplatin by promoting ferroptosis in BC cells. Mechanistically, SND1 was revealed to bind to the 3'UTR region of GPX4 mRNA and stabilise it. Knockdown of GPX4 could also overcome chemoresistance, and overexpressing GPX4 reversed the effects of silencing of GPX4 on the chemosensitivity of BC cells. Thus, targeting the SND1‑GPX4 axis may be a potential strategy to overcome chemoresistance in BC cells.
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January-2023
Volume 49 Issue 1

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Zhao Y, Ren P, Yang Z, Wang L and Hu C: Inhibition of SND1 overcomes chemoresistance in bladder cancer cells by promoting ferroptosis. Oncol Rep 49: 16, 2023.
APA
Zhao, Y., Ren, P., Yang, Z., Wang, L., & Hu, C. (2023). Inhibition of SND1 overcomes chemoresistance in bladder cancer cells by promoting ferroptosis. Oncology Reports, 49, 16. https://doi.org/10.3892/or.2022.8453
MLA
Zhao, Y., Ren, P., Yang, Z., Wang, L., Hu, C."Inhibition of SND1 overcomes chemoresistance in bladder cancer cells by promoting ferroptosis". Oncology Reports 49.1 (2023): 16.
Chicago
Zhao, Y., Ren, P., Yang, Z., Wang, L., Hu, C."Inhibition of SND1 overcomes chemoresistance in bladder cancer cells by promoting ferroptosis". Oncology Reports 49, no. 1 (2023): 16. https://doi.org/10.3892/or.2022.8453