因子抑制HIF（FIH）是一种阿斯巴拉胺羟化酶，作用于低氧诱导因子（HIF）以控制细胞对低氧环境的适应能力。FIH在多种肿瘤类型中表达，但其在肿瘤进展中的影响尚未得到广泛探索。我们观察到FIH在人类肺癌组织中有表达。在小鼠和人类肺癌细胞中删除FIH导致糖酵解代谢增加，与HIF活性增加一致。FIH缺乏的肺癌细胞表现出减少的增殖能力。RNA-seq数据的分析确认了细胞周期和存活方面的变化，并揭示了FIH缺失导致的分子通路失调，包括Hippo肿瘤抑制通路的关键成分血管动力素（Amot）的上调。我们表明，与FIH能力的肿瘤相比，FIH缺乏的肿瘤表现出更高的NK和T细胞免疫浸润。体内研究表明，FIH缺失导致肿瘤生长和转移能力降低。此外，高表达FIH与非小细胞肺癌（NSCLC）的整体生存率较差相关。综上所述，我们的数据揭示了FIH作为肺癌治疗的一个治疗靶点。

Factor inhibiting HIF (FIH) is an asparagine hydroxylase that acts on hypoxia inducible factors (HIFs) to control cellular adaptation to hypoxia. FIH is expressed in several tumor types, but its impact in tumor progression remains largely unexplored. We observed that FIH was expressed on human lung cancer tissue. Deletion of FIH in mouse and human lung cancer cells resulted in an increased glycolytic metabolism, consistent with increased HIF activity. FIH-deficient lung cancer cells exhibited decreased proliferation. Analysis of RNA-seq data confirmed changes in the cell cycle and survival, and revealed molecular pathways that were dysregulated in the absence of FIH including the upregulation of angiomotin (Amot), a key component of the Hippo tumor suppressor pathway. We show that FIH-deficient tumors were characterized by higher immune infiltration of NK and T cells compared to FIH competent tumor cells. In vivo studies demonstrated that FIH deletion resulted in reduced tumor growth and metastatic capacity. Moreover, high FIH expression correlated with poor overall survival in non-small cell lung cancer (NSCLC). Together, our data unravel FIH as a therapeutic target for the treatment of lung cancer.