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Remodelin, an Inhibitor of NAT10, Could Suppress Hypoxia-induced or Constitutional Expression of HIFs in Cells

Overview
Publisher Springer
Specialty Biochemistry
Date 2020 Jun 13
PMID 32529496
Citations 10
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Abstract

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 (CoCl) 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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References
1.
Semenza G . Hypoxia-inducible factors in physiology and medicine. Cell. 2012; 148(3):399-408. PMC: 3437543. DOI: 10.1016/j.cell.2012.01.021. View

2.
Wu D, Potluri N, Lu J, Kim Y, Rastinejad F . Structural integration in hypoxia-inducible factors. Nature. 2015; 524(7565):303-8. DOI: 10.1038/nature14883. View

3.
Swartz J, Pothen A, Stegeman I, Willems S, Grolman W . Clinical implications of hypoxia biomarker expression in head and neck squamous cell carcinoma: a systematic review. Cancer Med. 2015; 4(7):1101-16. PMC: 4529348. DOI: 10.1002/cam4.460. View

4.
Kaelin Jr W, Ratcliffe P . Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell. 2008; 30(4):393-402. DOI: 10.1016/j.molcel.2008.04.009. View

5.
Prager G, Poettler M . Angiogenesis in cancer. Basic mechanisms and therapeutic advances. Hamostaseologie. 2011; 32(2):105-14. DOI: 10.5482/ha-1163. View