Background. Hepatoblastoma (HB) is the most common liver malignancy in pediatrics, but the treatment for this disease is minimal. This study is aimed at exploring the effect of FoxO1 and SREBP-1c on HB and their mechanism. Methods. FoxO1, SREBP-1c, FASN, ACLY, ACC, and MAGL expressions in tissue samples were detected by RT-qPCR and WB. IHC was utilized to measure FASN content. Overexpression and knockdown of FoxO1 and sSREBP-1c were performed on Huh-6 cells. Cell proliferation, migration, and invasion were examined by CCK8, scratch, and transwell assay. ELISA was performed to test the ATP, FAO, NEFA, and Acetyl-CoA contents. ChIP was used to detect the interaction between SREBP-1c protein and the FoxO1 gene. In vivo tumorigenesis was conducted on mice. The morphology of tumor tissue sections was observed by HE staining. Results. FoxO1 expression was downregulated in HB tissue, while the expressions of SREBP-1c, FASN, ACLY, ACC, and MAGL were upregulated. In Huh-6 cells and mouse tumor tissues, FoxO1 knockdown resulted in increased cell proliferation, migration, and invasion and active fatty acid metabolism. On the contrary, after the knockdown of SREBP-1c, cell proliferation, migration, and invasion were weakened, and fatty acid metabolism was significantly reduced. SREBP-1c interacted with the promoter of the FoxO1 gene. When FoxO1 was knocked down, the tumor tissue was more closely packed. After the knockdown of the SREBP-1c gene, the structure of tumor cells was deformed. Conclusion. FoxO1 and SREBP-1c inhibited each other in HB, leading to the increase of intracellular fatty acid metabolism, and ultimately facilitated the development of HB.

中文翻译：

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FoxO1和SREBP-1c的相互抑制通过调节脂肪酸代谢来调节肝母细胞瘤的进展

背景。肝母细胞瘤 (HB) 是儿科中最常见的肝脏恶性肿瘤，但对该病的治疗很少。本研究旨在探讨 FoxO1 和 SREBP-1c 对 HB 的影响及其机制。方法. 通过 RT-qPCR 和 WB 检测组织样本中 FoxO1、SREBP-1c、FASN、ACLY、ACC 和 MAGL 的表达。IHC 用于测量 FASN 含量。在 Huh-6 细胞上进行 FoxO1 和 sSREBP-1c 的过表达和敲低。通过 CCK8、scratch 和 transwell 测定检查细胞增殖、迁移和侵袭。进行 ELISA 以测试 ATP、FAO、NEFA 和乙酰辅酶 A 含量。ChIP 用于检测 SREBP-1c 蛋白与 FoxO1 基因之间的相互作用。对小鼠进行体内肿瘤发生。HE染色观察肿瘤组织切片形态。结果. HB组织中FoxO1表达下调，而SREBP-1c、FASN、ACLY、ACC和MAGL表达上调。在 Huh-6 细胞和小鼠肿瘤组织中，FoxO1 敲低导致细胞增殖、迁移和侵袭增加以及脂肪酸代谢活跃。相反，敲低SREBP-1c后，细胞增殖、迁移和侵袭能力减弱，脂肪酸代谢明显降低。SREBP-1c 与 FoxO1 基因的启动子相互作用。当 FoxO1 被击倒时，肿瘤组织更加紧密。SREBP-1c基因敲低后，肿瘤细胞结构发生变形。结论. FoxO1和SREBP-1c在HB中相互抑制，导致细胞内脂肪酸代谢增加，最终促进了HB的发展。