Hypoxia-inducible factors (HIFs) are key mediators expressed under hypoxic condition and involved in many kinds of disease such as cancer and abnormal angiogenesis. Thus, development of their inhibitor has been extensively explored. Here, we describe a finding that Remodelin, a specific inhibitor of NAT10, could also inhibit the expression of HIFs. The presence of Remodelin could suppress the elevated level of HIF-1α protein and its nuclear translocation induced by either treatment of cobalt chloride (CoCl₂) or hypoxia in dose or time-dependent way. More importantly, Remodelin could also inhibit the constitutional expression of HIF-1α and HIF-2α in VHL mutant 786-0 cells. With using of cells with depletion of NAT10 by shRNA or Crispr-Cas9 edited, we further demonstrated that inhibition of HIFs by Remodelin should need NAT10 activity. In biological analysis, the treatment of cultured HUVECs with Remodelin could inhibit in vitro cell migration and invasion and tube-formation. Our investigation implied that Remodelin could be a new potential inhibitor of HIFs for using in angiogenesis targeting therapy in either cancers or inflammatory diseases.

缺氧诱导因子（HIFs）是在低氧条件下表达的关键介质，参与多种疾病，例如癌症和异常血管生成。因此，已经广泛探索了其抑制剂的开发。在这里，我们描述了一个发现，即NAT10的特异性抑制剂Remodelin也可以抑制HIF的表达。Remodelin的存在可以抑制HIF-1α蛋白的升高水平及其通过氯化钴（CoCl ₂）或剂量依赖性或时间依赖性的缺氧。更重要的是，Remodelin还可以抑制VHL突变786-0细胞中HIF-1α和HIF-2α的结构表达。通过使用shRNA或Crispr-Cas9编辑的具有耗尽NAT10的细胞，我们进一步证明了通过Remodelin抑制HIF应该需要NAT10活性。在生物学分析中，用Remodelin处理培养的HUVEC可以抑制体外细胞迁移，侵袭和管形成。我们的研究表明，Remodelin可能是一种新的潜在的HIF抑制剂，可用于癌症或炎症性疾病的血管生成靶向治疗。