顺铂是胃癌（GC）的一线化疗药物。然而，化疗抗性的发展使得顺铂的疗效受到阻碍，导致GC患者预后不佳。最近的证据表明，循环RNA（circRNA）和自噬依赖性的铁死亡异常调控在肿瘤化疗抗性中起到重要作用。在此，我们首次报告循环HIPK3在GC顺铂抗性中具有重要作用。循环HIPK3通过调节自噬和铁死亡异常来调控顺铂抗性。简而言之，沉默循环HIPK3通过miR-508-3p/Bcl-2/beclin1/SLC7A11通路增强铁死亡异常，降低GC细胞对顺铂的抗性。综上所述，我们的结果表明铁死亡异常是改善顺铂抗性的一种有前景的策略。重要的是，血清外泌体循环HIPK3也可以作为一种非侵入性指标来评估GC的顺铂抗性。© 2023 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC.

Cisplatin is the first-line chemotherapy for gastric cancer (GC). However, its efficacy is dampened by the development of chemoresistance, which leads to poor prognosis in GC patients. Recently, evidence has revealed that circular RNAs (circRNAs) and dysregulation of autophagy-dependent ferroptosis play critical roles in cancer chemoresistance. Herein, for the first time we report that circHIPK3 has a vital role in GC cisplatin resistance. CircHIPK3 regulated cisplatin resistance by targeting autophagy and ferroptosis. In brief, knockdown circHIPK3 decreased GC cell cisplatin resistance by enhancing ferroptosis via the miR-508-3p/Bcl-2/beclin1/SLC7A11 axis. Taken together, our results demonstrate that ferroptosis is a promising strategy to ameliorate cisplatin resistance. Importantly, serum exosomal circHIPK3 could also be a noninvasive indicator to evaluate cisplatin resistance in GC.© 2023 The Authors. Journal of Cellular Physiology published by Wiley Periodicals LLC.