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Background <p>The contribution of USP22 in NPC chemoresistance and stemness remains unknown, especially under hypoxic conditions.</p> Objective <p>To investigate the function and potential mechanism of hypoxia-induced USP22 in chemoresistance and cell stemness in nasopharyngeal carcinoma (NPC).</p> Results <p>Following the exposure of NPC cells to hypoxia and normoxia, USP22 expression in NPC cells exhibited more sensitivity under hypoxia compared to normoxia and was enhanced in a time-dependent manner. Cisplatin IC50 was markedly elevated under hypoxia compared to normoxia, and hypoxia greatly enhanced NPC cell migration and stemness, whereas USP22 knockdown reversed these hypoxia-induced changes. USP22 overexpression facilitated glycolysis under hypoxia, and the glycolysis inhibitor 2-DG suppressed the enhancement of chemo-resistance and cell stemness induced by USP22 overexpression in the hyperoxia condition. Mechanistically, USP22 interacted with HIF-1α and enhanced its stability through deubiquitination.</p> Conclusion <p>Hypoxia-induced USP22 contributes to the maintenance of stemness and chemoresistance in NPC cells by stabilizing HIF-1α, which partly functions through glycolysis. Targeting USP22 might be an effective strategy to ameliorate NPC chemoresistance, especially in the hypoxic microenvironment.</p>

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Hypoxia-induced USP22 contributes to tumor stemness and chemoresistance in nasopharyngeal carcinoma via stabilizing HIF-1α

  • 期刊论文

  • 发表日期：

    2025年4月10日

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  • Ke Chen,
  • Shunxin Li

摘要

Background

The contribution of USP22 in NPC chemoresistance and stemness remains unknown, especially under hypoxic conditions.

Objective

To investigate the function and potential mechanism of hypoxia-induced USP22 in chemoresistance and cell stemness in nasopharyngeal carcinoma (NPC).

Results

Following the exposure of NPC cells to hypoxia and normoxia, USP22 expression in NPC cells exhibited more sensitivity under hypoxia compared to normoxia and was enhanced in a time-dependent manner. Cisplatin IC50 was markedly elevated under hypoxia compared to normoxia, and hypoxia greatly enhanced NPC cell migration and stemness, whereas USP22 knockdown reversed these hypoxia-induced changes. USP22 overexpression facilitated glycolysis under hypoxia, and the glycolysis inhibitor 2-DG suppressed the enhancement of chemo-resistance and cell stemness induced by USP22 overexpression in the hyperoxia condition. Mechanistically, USP22 interacted with HIF-1α and enhanced its stability through deubiquitination.

Conclusion

Hypoxia-induced USP22 contributes to the maintenance of stemness and chemoresistance in NPC cells by stabilizing HIF-1α, which partly functions through glycolysis. Targeting USP22 might be an effective strategy to ameliorate NPC chemoresistance, especially in the hypoxic microenvironment.