本研究旨在探讨SF3B1在非小细胞肺癌中的表达及其临床意义、生物学功能和分子机制。根据 TCGA 数据和免疫组织化学，肺鳞状细胞癌和肺腺癌 (LUAD) 组织中 SF3B1 mRNA 和蛋白水平均升高。值得注意的是，LUAD 中 SF3B1 的高表达与淋巴结转移增加显着相关。涉及 SF3B1 敲低和过表达的功能实验表明 SF3B1 促进 LUAD 细胞的增殖、侵袭和迁移。此外，SF3B1 抑制剂 pladienolide-B 在体外和体内均减弱了 LUAD 细胞的攻击行为。 RNA测序分析表明，与各自的对照组相比，SF3B1敲低组和SF3B1抑制剂组中的差异表达基因在铁死亡相关通路中富集。通过检测谷胱甘肽消耗、脂质过氧化以及使用透射电子显微镜观察形态变化，验证了 SF3B1 在 LUAD 细胞中的抗铁死亡作用。这一过程被证实独立于细胞凋亡和自噬，铁死亡诱导剂erastin、细胞凋亡抑制剂Z-VAD-FMK和自噬抑制剂3-甲基腺嘌呤的作用证明了这一点。拯救实验表明，LUAD 中 SF3B1 的抗铁死亡作用部分是通过上调 SLC7A11 的表达来介导的。© 2024。作者获得 Springer Nature America, Inc. 的独家许可。

This study aimed to investigate the expression of SF3B1 in non-small cell lung cancer, and its clinical significance, biological function, and molecular mechanisms. SF3B1 mRNA and protein levels were elevated in both lung squamous cell carcinoma and lung adenocarcinoma (LUAD) tissues based on TCGA data and immunohistochemistry. Notably, high SF3B1 expression in LUAD was significantly associated with increased lymph node metastasis. Functional experiments involving SF3B1 knockdown and overexpression demonstrated that SF3B1 facilitated the proliferation, invasion, and migration of LUAD cells. Additionally, the SF3B1 inhibitor pladienolide-B attenuated the aggressive behavior of LUAD cells both in vitro and in vivo. RNA sequencing analysis indicated that differentially expressed genes in the SF3B1 knockdown and SF3B1 inhibitor groups were enriched in ferroptosis-related pathways compared to their respective control groups. The antiferroptotic role of SF3B1 in LUAD cells was validated by detecting glutathione depletion, lipid peroxidation, and observing morphological changes using transmission electron microscopy. This process was confirmed to be independent of apoptosis and autophagy, as evidenced by the effects of the ferroptosis inducer erastin, the apoptosis inhibitor Z-VAD-FMK, and the autophagy inhibitor 3-methyladenine. Rescue experiments indicated that the antiferroptotic role of SF3B1 in LUAD is partially mediated by upregulating the expression of SLC7A11.© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.