Remodelin, an inhibitor of NAT10, could suppress hypoxia-induced or constitutional expression of HIFs in cells
Remodelin, an inhibitor of NAT10, could suppress hypoxia-induced or constitutional expression of HIFs in cells
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Remodelin 是 NAT10 的抑制剂，可以抑制细胞中缺氧诱导的 HIF 或体质表达
DOI：
10.1007/s11010-020-03776-w
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发表时间：
2020-06
期刊：
影响因子：
--
通讯作者：
张波
中科院分区：
文献类型：
--
作者：
吴雅倩;曹亚楠;刘海静;姚孟飞;马宁宁;张波
缺氧诱导因子（HIFs）是在缺氧条件下表达的关键介质，涉及多种疾病，如癌症和异常血管生成。因此，其抑制剂的开发已得到广泛探索。在此，我们描述了一项发现，即NAT10的特异性抑制剂Remodelin也能够抑制HIFs的表达。Remodelin的存在能够以剂量或时间依赖的方式抑制氯化钴（CoCl₂）处理或缺氧诱导的HIF - 1α蛋白水平升高及其核转位。更重要的是，Remodelin还能够抑制VHL突变的786 - 0细胞中HIF - 1α和HIF - 2α的组成性表达。通过使用shRNA或CRISPR - Cas9编辑的NAT10缺失细胞，我们进一步证明Remodelin对HIFs的抑制需要NAT10的活性。在生物学分析中，用Remodelin处理培养的人脐静脉内皮细胞（HUVECs）能够抑制体外细胞迁移、侵袭和管形成。我们的研究表明，Remodelin可能是一种新的潜在的HIFs抑制剂，可用于癌症或炎症性疾病的血管生成靶向治疗。
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.
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影响因子：
16.6
作者：
Balmus G;Larrieu D;Barros AC;Collins C;Abrudan M;Demir M;Geisler NJ;Lelliott CJ;White JK;Karp NA;Atkinson J;Kirton A;Jacobsen M;Clift D;Rodriguez R;Sanger Mouse Genetics Project;Adams DJ;Jackson SP
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Jackson SP
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2.9
作者：
Luo Y;Na Z;Slavoff SA
通讯作者：
Slavoff SA
影响因子：
14.9
作者：
Sharma S;Langhendries JL;Watzinger P;Kötter P;Entian KD;Lafontaine DL
通讯作者：
Lafontaine DL
影响因子：
4.8
作者：
Yuan, Y;Hilliard, G;Millhorn, DE
通讯作者：
Millhorn, DE
影响因子：
64.8
作者：
Maxwell, PH;Wiesener, MS;Ratcliffe, PJ
通讯作者：
Ratcliffe, PJ