张澳归,徐芹芹

铁死亡是一种新型的细胞死亡方式，与多种癌症的发生和发展密切相关，尤其是在肺腺癌中，其机制尚未完全阐明。近年来，SENP1（SUMO特异性蛋白酶1）作为一种重要的调控因子，逐渐被发现与铁死亡过程密切相关，成为研究的热点。SENP1在细胞内通过调节SUMO化修饰影响多个信号通路，进而影响细胞的铁代谢和氧化应激状态。研究表明，SENP1的表达变化能够显著影响肺腺癌细胞的生存与死亡，提示其在铁死亡中的重要作用。然而，关于SENP1具体如何介导这些过程、以及其在肺腺癌治疗中的潜在应用仍需进一步探讨。通过综述SENP1在肺腺癌细胞铁死亡中的修饰作用及其潜在机制，本文旨在为肺腺癌的治疗提供新的思路和靶点，为未来的研究奠定基础。

SENP1；肺腺癌；铁死亡；调控机制；细胞信号通路

[1] Ko MJ,Min S,Hong H,et al.Magnetic nanoparticles for ferroptosis cancer therapy with diagnostic imaging.Bioact Mater.32:66-97. [2] Yang H,Zhao L,Gao Y,et al.Pharmacotranscriptomic Analysis Reveals Novel Drugs and Gene Networks Regulating Ferroptosis in Cancer.Cancers(Basel).2020;12(11). [3] Zhou Q,Meng Y,Li D,et al.Ferroptosis in cancer:From molecular mechanisms to therapeutic strategies.Signal Transduct Target Ther.2024;9(1):55. [4] Chuang YT,Yen CY,Chien TM,et al.Ferroptosis-Regulated Natural Products and miRNAs and Their Potential Targeting to Ferroptosis and Exosome Biogenesis.Int J Mol Sci.2024;25(11). [5] Shan C,Liang Y,Wang K,Li P.Noncoding RNAs in cancer ferroptosis:From biology to clinical opportunity.Biomed Pharmacother.165:115053. [6] Liu X,Wang L,Xi X,Zhou T,Sun Z,Zhang B.Targeting ferroptosis:a novel insight into thyroid cancer therapy.Front Endocrinol (Lausanne).16:1527693. [7] Xu X,Mao Y,Feng Z,Dai F,Gu T,Zheng J.SENP1 inhibits ferroptosis and promotes head and neck squamous cell carcinoma by regulating ACSL4 protein stability via SUMO1.Oncol Rep.2024;51(2). [8] Dong J,Zheng X.SENP1 knockdown potentiates the apoptosis,cell cycle arrest,and reduces cisplatin resistance of diffuse large B cell lymphoma cells via inducing ferroptosis.Biochem Cell Biol.2024;102(4):319-330. [9] Chen Y,Chen B,Hong Y,Chen L,Zheng S.SENP1 promotes deacetylation of isocitrate dehydrogenase 2 to inhibit ferroptosis of breast cancer via enhancing SIRT3 stability.Biotechnol Appl Biochem.2025;72(3):805-824. [10] Wang DG,Wang J,Gao J,et al.Circ_0002638 drives squamous cell lung cancer(LUSC)progression and chemotherapy resistance by inhibiting ferroptosis via SENP1-mediated deSUMOylation of ACSL4.Life Sci. [11] Bai YT,Xiao FJ,Wang H,Ge RL,Wang LS.Hypoxia protects H9c2 cells against Ferroptosis through SENP1-mediated protein DeSUMOylation.Int J Med Sci.2021;18(7):1618-1627. [12] Song KP,Shu P,Ma JL,Wang B,Chen B.[Ribosomal Protein S9 Expression in Multiple Myeloma and Its Effect on Cell Biological Function].Zhongguo Yi Xue Ke Xue Yuan Xue Bao.2019;41(2):175-182. [13] Xiong J,Chen P,He L,Chai X,Zhang Y,Sun S.Functional mechanism of hypoxia-like conditions mediating resistance to ferroptosis in cervical cancer cells by regulating KDM4A SUMOylation and the SLC7A11/GPX4 pathway.Environ Toxicol.2024;39(8):4207-4220. [14] Liu M,Kong XY,Yao Y,et al.The critical role and molecular mechanisms of ferroptosis in antioxidant systems:a narrative review.Ann Transl Med.2022;10(6):368. [15] Zhang L,Luo YL,Xiang Y,et al.Ferroptosis inhibitors:past,present and future.Front Pharmacol.15:1407335. [16] Fang XL,Ding SY,Du XZ,Wang JH,Li XL.Ferroptosis-A Novel Mechanism With Multifaceted Actions on Stroke.Front Neurol. 13:881809. [17] Wang Y,Fleishman JS,Li Y,et al.Non‑coding RNA‑mediated epigenetic modification of ferroptosis in non‑small cell lung cancer (Review).Int J Oncol.2025;66(1). [18] Zhou LP,Zhang RJ,Jia CY,et al.Ferroptosis:A potential target for the intervention of intervertebral disc degeneration.Front Endocrinol(Lausanne).13:1042060. [19] Luo J,Song G,Chen N,et al.Ferroptosis contributes to ethanol-induced hepatic cell death via labile iron accumulation and GPx4 inactivation.Cell Death Discov.2023;9(1):311. [20] Gao C,Xiao F,Zhang L,et al.SENP1 inhibition suppresses the growth of lung cancer cells through activation of A20-mediated ferroptosis[J].Annals of Translational Medicine,2022,10(4):224.

点击下载PDF