Department of Radiation Oncology, Hainan General Hospital, Hainan Affiliated Hospital of Hainan Medical University, Haikou City, 570311, Hainan Province, China.
Department of Radiation Oncology, Hainan Affiliated Hospital of Hainan Medical University, Haikou City, Hainan Province, China.
Sci Rep. 2024 Aug 28;14(1):19948. doi: 10.1038/s41598-024-70970-x.
Non-small cell lung cancer (NSCLC), being the most prevalent and lethal malignancy affecting the lungs, poses a significant threat to human health. This research aims at illustrating the precise role and related mechanisms of silent information regulator type-1 (SIRT1) in NSCLC progression. The expression pattern of SIRT1 in NSCLC cell lines was examined using quantitative real-time polymerase chain reaction and western blotting. Functional assays in NSCLC cell lines validated the biological capabilities of SIRT1 on malignant phenotypes, and its impact on tumorigenicity was further evaluated in vivo. In addition, the FOXO1 inhibitor AS1842856 was applied to verify the role of SIRT1 on FOXO pathway in vitro. SIRT1 expression was prominently elevated in NSCLC cell lines. The depletion of SIRT1 retarded the capabilities of proliferation, migration and invasion, while enhancing apoptosis in NSCLC cells. Furthermore, SIRT1 silencing restricted the tumorigenesis of NSCLC in vivo. Additionally, AS1842856 treatment ameliorated the inhibitory effect of SIRT1 deficiency on malignant phenotypes in NSCLC cells. SIRT1 deletion exerted an anti-oncogenic role in NSCLC via activation of FOXO1.
非小细胞肺癌(NSCLC)是最常见和最致命的肺部恶性肿瘤,严重威胁着人类健康。本研究旨在阐明沉默信息调节因子 1(SIRT1)在非小细胞肺癌进展中的精确作用及相关机制。采用实时定量聚合酶链反应和 Western blot 检测 SIRT1 在 NSCLC 细胞系中的表达模式。在 NSCLC 细胞系中的功能研究验证了 SIRT1 对恶性表型的生物学功能,进一步在体内评估了其对致瘤性的影响。此外,还应用 FOXO1 抑制剂 AS1842856 验证了 SIRT1 对 FOXO 通路的作用。结果显示,SIRT1 在 NSCLC 细胞系中表达明显升高。沉默 SIRT1 可减缓 NSCLC 细胞的增殖、迁移和侵袭能力,同时促进细胞凋亡。此外,SIRT1 沉默可抑制 NSCLC 细胞在体内的致瘤性。此外,AS1842856 处理可改善 SIRT1 缺陷对 NSCLC 细胞恶性表型的抑制作用。SIRT1 缺失通过激活 FOXO1 在 NSCLC 中发挥抑癌作用。