Background and Objective: Lung cancer is a prevalent global malignancy, and investigating the metabolic reprogramming of tumor cells has significant therapeutic implications. This study aims to explore the molecular mechanism driving the progression of non-small cell lung cancer (NSCLC), with a specific emphasis on the STAT3-ACC1-FAS axis involved in fatty acid synthesis./nMethods: The levels of Signal transducer and activator of transcription 3 (STAT3) and acetyl-CoA carboxylase 1 (ACC1) were determined in mouse NSCLC specimens and cell lines using Western blot and qPCR methods. Various assays such as CCK-8, colony formation, EDU, wound-healing, and transwell migration were employed to assess cancer cell proliferation, migration, and invasion. Additionally, a nude mouse xenograft model was utilized for in vivo tumor growth analysis. The interaction between STAT3 and ACC1 was examined through chromatin immunoprecipitation and dual-luciferase assays./nResults: The study observed upregulation of STAT3 and ACC1 in NSCLC tissues. Notably, the suppression of STAT3 and ACC1 inhibited the in vitro progression and lipid synthesis of NSCLC cells. Furthermore, STAT3 enhanced lipid synthesis by upregulating ACC1 expression. Mechanistic assays revealed that this process occurred through direct activation of ACC1 transcription by STAT3. STAT3 played a vital role in regulating lipid metabolism and supporting NSCLC progression./nConclusion: The findings of this study underscore the significance of the STAT3-ACC1-FAS axis in NSCLC. The activation of ACC1 through STAT3-mediated transcription serves as a crucial mechanism for stimulating the progression of NSCLC tumors and promoting lipid synthesis. Consequently, targeting the STAT3-ACC1 axis may present a promising avenue for the diagnosis and treatment of NSCLC patients.

中文翻译：

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揭示STAT3-ACC1轴：非小细胞肺癌脂质代谢和肿瘤进展的关键驱动因素

背景和目的：肺癌是一种普遍存在的全球恶性肿瘤，研究肿瘤细胞的代谢重编程具有重要的治疗意义。本研究旨在探讨驱动非小细胞肺癌（NSCLC）进展的分子机制，特别关注参与脂肪酸合成的 STAT3-ACC1-FAS 轴。/n方法：信号转导器和信号转导器的水平使用蛋白质印迹和 qPCR 方法测定小鼠 NSCLC 样本和细胞系中的转录激活子 3 (STAT3) 和乙酰辅酶 A 羧化酶 1 (ACC1)。采用CCK-8、集落形成、EDU、伤口愈合和跨孔迁移等各种测定来评估癌细胞增殖、迁移和侵袭。此外，还利用裸鼠异种移植模型进行体内肿瘤生长分析。通过染色质免疫沉淀和双荧光素酶测定检查 STAT3 和 ACC1 之间的相互作用。/n结果：研究观察到 NSCLC 组织中 STAT3 和 ACC1 的上调。值得注意的是，抑制 STAT3 和 ACC1 可抑制NSCLC 细胞的体外进展和脂质合成。此外，STAT3 通过上调 ACC1 表达来增强脂质合成。机制分析表明，这一过程是通过 STAT3 直接激活 ACC1 转录而发生的。STAT3 在调节脂质代谢和支持 NSCLC 进展中发挥着至关重要的作用。/n结论：本研究的结果强调了 STAT3-ACC1-FAS 轴在 NSCLC 中的重要性。通过 STAT3 介导的转录激活 ACC1 是刺激 NSCLC 肿瘤进展和促进脂质合成的关键机制。因此，靶向 STAT3-ACC1 轴可能为 NSCLC 患者的诊断和治疗提供一条有希望的途径。