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（HIF）是缺氧条件下表达的关键介质，参与癌症、异常血管生成等多种疾病。因此，其抑制剂的开发已被广泛探索。在这里，我们描述了一项发现，即 NAT10 的特异性抑制剂 Remodelin 也可以抑制 HIF 的表达。 Remodelin 的存在可以抑制氯化钴 (CoCl ₂ ) 处理或缺氧引起的 HIF-1α 蛋白水平升高及其核转位，且呈剂量或时间依赖性。更重要的是，Remodelin还可以抑制VHL突变786-0细胞中HIF-1α和HIF-2α的表达。通过使用通过 shRNA 或 Crispr-Cas9 编辑而耗尽 NAT10 的细胞，我们进一步证明 Remodelin 对 HIF 的抑制应该需要 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 HIF 抑制剂，可用于癌症或炎症性疾病的血管生成靶向治疗。