肝细胞癌（HCC）是全球癌症相关死亡的第二大原因，每年死亡人数超过80万人，其5年生存率不到12%。尽管 HN1 基因在多种癌症类型中表达上调，但其在 HCC 中的作用仍然难以捉摸。在我们的研究中，我们发现 HN1 在 HCC 组织中表达升高，过度表达后会促进细胞增殖、迁移和侵袭，揭示其作为 HCC 癌基因的作用。此外，沉默 HN1 会降低 HCC 细胞的活力和转移，而 HN1 过度表达则会刺激其生长和侵袭。基因表达谱显示，HN1 沉默下调了 379 个基因，上调了 130 个基因，以及与脂肪生成信号通路网络相关的抑制蛋白。值得注意的是，抑制 HN1 会显着降低 SREBP1 和 SREBP2 的表达水平，而升高 HN1 则会产生相反的效果。 HN1 的这种双重调节影响脂质形成，在 HN1 沉默时阻碍脂质形成，在 HN1 过表达时促进脂质形成。此外，HN1 触发 Akt 通路，通过 SREBP1 介导的脂肪生成促进肿瘤发生，沉默 HN1 通过失活 SREBP-1 有效抑制小鼠异种移植模型中的 HCC 肿瘤生长，强调了 HN1 作为治疗靶点的潜力，影响外部和内部因素，它有望成为 HCC 的有效治疗策略。© 2024。作者获得 Springer Nature America, Inc. 的独家许可。

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related deaths worldwide, with more than 800,000 deaths each year, and its 5-year survival rate is less than 12%. The role of the HN1 gene in HCC has remained elusive, despite its upregulation in various cancer types. In our investigation, we identified HN1's heightened expression in HCC tissues, which, upon overexpression, fosters cell proliferation, migration, and invasion, unveiling its role as an oncogene in HCC. In addition, silencing HN1 diminished the viability and metastasis of HCC cells, whereas HN1 overexpression stimulated their growth and invasion. Gene expression profiling revealed HN1 silencing downregulated 379 genes and upregulated 130 genes, and suppressive proteins associated with the lipogenic signaling pathway networks. Notably, suppressing HN1 markedly decreased the expression levels of SREBP1 and SREBP2, whereas elevating HN1 had the converse effect. This dual modulation of HN1 affected lipid formation, hindering it upon HN1 silencing and promoting it upon HN1 overexpression. Moreover, HN1 triggers the Akt pathway, fostering tumorigenesis via SREBP1-mediated lipogenesis and silencing HN1 effectively curbed HCC tumor growth in mouse xenograft models by deactivating SREBP-1, emphasizing the potential of HN1 as a therapeutic target, impacting both external and internal factors, it holds promise as an effective therapeutic strategy for HCC.© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.