射频消融（RFA）是一种有效且可行的肺癌治疗方法，但不完全射频消融（RFA）后残留非小细胞肺癌（NSCLC）加速进展的报道屡见不鲜。之前的一项研究报告称，HSP70 和 HIF-1α 在 RFA 不完整的区域高表达。因此，我们试图阐明HIF-1α/HSP70通路对不完全射频消融后肺癌复发的调节作用。在本研究中，我们发现敲低HSP70可以减少HIF-1α的sumo 1、sumo 2/3（SUMO化标记物）并抑制热应激条件下（用于体外模拟不完全RFA）下A549细胞的增殖和迁移。我们观察到HSP70的敲低改变了铁死亡相关蛋白和基因（SLC7A11和ACSL3）的表达，RNA-seq结果显示HSP70的敲低激活了铁死亡途径，进一步证实了HSP70调节铁死亡。总之，HSP70通过HIF-1α SUMO化，抑制铁死亡，诱导射频消融后肺癌复发。该研究为进一步研究抑制肺癌复发的治疗靶点揭示了新的方向，为进一步的临床研究提供了理论基础。版权所有：©2023 Peng et al.这是一篇根据知识共享署名许可条款分发的开放获取文章，允许在任何媒体上不受限制地使用、分发和复制，前提是注明原始作者和来源。

Radiofrequency ablation (RFA) is an effective and feasible therapy for lung cancer, but accelerated progression of residual non-small cell lung cancer (NSCLC) after incomplete radiofrequency ablation (RFA) has frequently been reported. A previous study reported that HSP70 and HIF-1α were highly expressed in areas with incomplete RFA. Therefore, we sought to elucidate the regulatory effect of the HIF-1α/HSP70 pathway on lung cancer recurrence after incomplete radiofrequency ablation. In this study, we found that knockdown of HSP70 can reduce sumo 1, sumo 2/3 (marker of SUMOylation) of HIF-1α and inhibit A549 cell proliferation and migration under heat stress conditions (used to simulate incomplete RFA in vitro). We observed that knockdown of HSP70 altered the expression of ferroptosis-related proteins and genes (SLC7A11 and ACSL3), and the RNA-seq results showed that knockdown of HSP70 activated the ferroptosis pathway, further confirming that HSP70 regulates ferroptosis. In summary, HSP70, via HIF-1α SUMOylation, inhibited ferroptosis, inducing lung cancer recurrence after radiofrequency ablation. The study reveals a new direction for further research on therapeutic targets to suppress lung cancer recurrence and provides a theoretical foundation for further clinical studies.Copyright: © 2023 Peng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.