Skip to main content
SpringerLink
Log in

Remodelin, an inhibitor of NAT10, could suppress hypoxia-induced or constitutional expression of HIFs in cells

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

A Correction to this article was published on 07 July 2020

This article has been updated

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 (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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Change history

  • 07 July 2020

    The article “Remodelin, an inhibitor of NAT10, could suppress hypoxia-induced or constitutional expression of HIFs in cells”, written by “Yaqian Wu, Yanan Cao, Haijing Liu, Mengfei Yao, Ningning Ma and Bo Zhang”, was originally published electronically on the publisher's internet portal https://link.springer.com/article/10.1007/s11010-020-03776-w on 11 June 2020 with open access. With the author(s)' decision to step back from Open Choice, the copyright of the article changed on 6 July 2020 to © Springer Science+Business Media, LLC, part of Springer Nature 2020 and the article is forthwith distributed under the terms of copyright. The original article has been corrected.

References

  1. Semenza GL (2012) Hypoxia-inducible factors in physiology and medicine. Cell 148(3):399–408. https://doi.org/10.1016/j.cell.2012.01.021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Wu D, Potluri N, Lu J, Kim Y, Rastinejad F (2015) Structural integration in hypoxia-inducible factors. Nature 524(7565):303–308. https://doi.org/10.1038/nature14883

    Article  CAS  PubMed  Google Scholar 

  3. Swartz JE, Pothen AJ, Stegeman I, Willems SM, Grolman W (2015) Clinical implications of hypoxia biomarker expression in head and neck squamous cell carcinoma: a systematic review. Cancer Med 4(7):1101–1116. https://doi.org/10.1002/cam4.460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kaelin WG Jr, Ratcliffe PJ (2008) Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell 30(4):393–402. https://doi.org/10.1016/j.molcel.2008.04.009

    Article  CAS  PubMed  Google Scholar 

  5. Prager GW, Poettler M (2012) Angiogenesis in cancer. Basic mechanisms and therapeutic advances. Hamostaseologie 32(2):105–114. https://doi.org/10.5482/ha-1163

    Article  CAS  PubMed  Google Scholar 

  6. Duan W, Chang Y, Li R, Xu Q, Lei J, Yin C, Li T, Wu Y, Ma Q, Li X (2014) Curcumin inhibits hypoxia inducible factor1alphainduced epithelialmesenchymal transition in HepG2 hepatocellular carcinoma cells. Mol Med Rep 10(5):2505–2510. https://doi.org/10.3892/mmr.2014.2551

    Article  CAS  PubMed  Google Scholar 

  7. Wang GL, Jiang BH, Rue EA, Semenza GL (1995) Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci USA 92(12):5510–5514. https://doi.org/10.1073/pnas.92.12.5510

    Article  CAS  PubMed  Google Scholar 

  8. Zhang H, Hou W, Wang HL, Liu HJ, Jia XY, Zheng XZ, Zou YX, Li X, Hou L, McNutt MA, Zhang B (2014) GSK-3beta-regulated N-acetyltransferase 10 is involved in colorectal cancer invasion. Clin Cancer Res 20(17):4717–4729. https://doi.org/10.1158/1078-0432.Ccr-13-3477

    Article  CAS  PubMed  Google Scholar 

  9. Lv J, Liu H, Wang Q, Tang Z, Hou L, Zhang B (2003) Molecular cloning of a novel human gene encoding histone acetyltransferase-like protein involved in transcriptional activation of hTERT. Biochem Biophys Res Commun 311(2):506–513. https://doi.org/10.1016/j.bbrc.2003.09.235

    Article  CAS  PubMed  Google Scholar 

  10. Shen Q, Zheng X, McNutt MA, Guang L, Sun Y, Wang J, Gong Y, Hou L, Zhang B (2009) NAT10, a nucleolar protein, localizes to the midbody and regulates cytokinesis and acetylation of microtubules. Exp Cell Res 315(10):1653–1667. https://doi.org/10.1016/j.yexcr.2009.03.007

    Article  CAS  PubMed  Google Scholar 

  11. Chi YH, Haller K, Peloponese JM Jr, Jeang KT (2007) Histone acetyltransferase hALP and nuclear membrane protein hsSUN1 function in de-condensation of mitotic chromosomes. J Biol Chem 282(37):27447–27458. https://doi.org/10.1074/jbc.M703098200

    Article  CAS  PubMed  Google Scholar 

  12. Larrieu D, Britton S, Demir M, Rodriguez R, Jackson SP (2014) Chemical inhibition of NAT10 corrects defects of laminopathic cells. Science 344(6183):527–532. https://doi.org/10.1126/science.1252651

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. 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, Adams DJ, Jackson SP (2018) Targeting of NAT10 enhances healthspan in a mouse model of human accelerated aging syndrome. Nat Commun 9(1):1700. https://doi.org/10.1038/s41467-018-03770-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Oh TI, Lee YM, Lim BO, Lim JH (2017) Inhibition of NAT10 suppresses melanogenesis and melanoma growth by attenuating microphthalmia-associated transcription factor (MITF) expression. Int J Mol Sci 18(9):1924. https://doi.org/10.3390/ijms18091924

    Article  CAS  PubMed Central  Google Scholar 

  15. Zhang X, Chen J, Jiang S, He S, Bai Y, Zhu L, Ma R, Liang X (2019) N-acetyltransferase 10 enhances doxorubicin resistance in human hepatocellular carcinoma cell lines by promoting the epithelial-to-mesenchymal transition. Oxid Med Cell Longev 2019:7561879. https://doi.org/10.1155/2019/7561879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Xiang X, Li C, Chen X, Dou H, Li Y, Zhang X, Luo Y (2019) CRISPR/Cas9-mediated gene tagging: a step-by-step protocol. Methods Mol Biol 1961:255–269. https://doi.org/10.1007/978-1-4939-9170-9_16

    Article  CAS  PubMed  Google Scholar 

  17. Prakash P, Lantz TC, Jethava KP, Chopra G (2019) Rapid, refined, and robust method for expression, purification, and characterization of recombinant human amyloid beta 1–42. Methods Protoc 2(2):48. https://doi.org/10.3390/mps2020048

    Article  CAS  PubMed Central  Google Scholar 

  18. Liu H, Ling Y, Gong Y, Sun Y, Hou L, Zhang B (2007) DNA damage induces N-acetyltransferase NAT10 gene expression through transcriptional activation. Mol Cell Biochem 300(1–2):249–258. https://doi.org/10.1007/s11010-006-9390-5

    Article  CAS  PubMed  Google Scholar 

  19. Maxwell PH, Wiesener MS, Chang GW, Clifford SC, Vaux EC, Cockman ME, Wykoff CC, Pugh CW, Maher ER, Ratcliffe PJ (1999) The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399(6733):271–275. https://doi.org/10.1038/20459

    Article  CAS  PubMed  Google Scholar 

  20. Xia M, Bi K, Huang R, Cho MH, Sakamuru S, Miller SC, Li H, Sun Y, Printen J, Austin CP, Inglese J (2009) Identification of small molecule compounds that inhibit the HIF-1 signaling pathway. Mol Cancer 8:117. https://doi.org/10.1186/1476-4598-8-117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Parker R, Sheth U (2007) P bodies and the control of mRNA translation and degradation. Mol Cell 25(5):635–646. https://doi.org/10.1016/j.molcel.2007.02.011

    Article  CAS  PubMed  Google Scholar 

  22. Luo Y, Na Z, Slavoff SA (2018) P-bodies: composition, properties, and functions. Biochemistry 57(17):2424–2431. https://doi.org/10.1021/acs.biochem.7b01162

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Fillman C, Lykke-Andersen J (2005) RNA decapping inside and outside of processing bodies. Curr Opin Cell Biol 17(3):326–331. https://doi.org/10.1016/j.ceb.2005.04.002

    Article  CAS  PubMed  Google Scholar 

  24. Anderson P, Kedersha N, Ivanov P (2015) Stress granules, P-bodies and cancer. Biochim Biophys Acta 1849(7):861–870. https://doi.org/10.1016/j.bbagrm.2014.11.009

    Article  CAS  PubMed  Google Scholar 

  25. Yuan Y, Hilliard G, Ferguson T, Millhorn DE (2003) Cobalt inhibits the interaction between hypoxia-inducible factor-alpha and von Hippel-Lindau protein by direct binding to hypoxia-inducible factor-alpha. J Biol Chem 278(18):15911–15916. https://doi.org/10.1074/jbc.M300463200

    Article  CAS  PubMed  Google Scholar 

  26. Ito S, Horikawa S, Suzuki T, Kawauchi H, Tanaka Y, Suzuki T, Suzuki T (2014) Human NAT10 is an ATP-dependent RNA acetyltransferase responsible for N4-acetylcytidine formation in 18 S ribosomal RNA (rRNA). J Biol Chem 289(52):35724–35730. https://doi.org/10.1074/jbc.C114.602698

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Sharma S, Langhendries JL, Watzinger P, Kotter P, Entian KD, Lafontaine DL (2015) Yeast Kre33 and human NAT10 are conserved 18S rRNA cytosine acetyltransferases that modify tRNAs assisted by the adaptor Tan1/THUMPD1. Nucleic Acids Res 43(4):2242–2258. https://doi.org/10.1093/nar/gkv075

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Arango D, Sturgill D, Alhusaini N, Dillman AA, Sweet TJ, Hanson G, Hosogane M, Sinclair WR, Nanan KK, Mandler MD, Fox SD, Zengeya TT, Andresson T, Meier JL, Coller J, Oberdoerffer S (2018) Acetylation of cytidine in mRNA promotes translation efficiency. Cell 175(7):1872–1886.e1824. https://doi.org/10.1016/j.cell.2018.10.030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Escuin D, Kline ER, Giannakakou P (2005) Both microtubule-stabilizing and microtubule-destabilizing drugs inhibit hypoxia-inducible factor-1alpha accumulation and activity by disrupting microtubule function. Cancer Res 65(19):9021–9028. https://doi.org/10.1158/0008-5472.Can-04-4095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Carbonaro M, O'Brate A, Giannakakou P (2011) Microtubule disruption targets HIF-1alpha mRNA to cytoplasmic P-bodies for translational repression. J Cell Biol 192(1):83–99. https://doi.org/10.1083/jcb.201004145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. This project was supported by Chinese National Natural Science Foundation (Grant Nos. 81872018, 81372292), and Key project from the Chinese Ministry of Science and Technology (Grant Nos. 2013YQ03065108, 2017YFC0110200).

Author information

Authors and Affiliations

  1. Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, 38 Xueyuan Road, Haidian District, Beijing, 100191, China

    Yaqian Wu, Yanan Cao, Haijing Liu, Mengfei Yao, Ningning Ma & Bo Zhang

Authors
  1. Yaqian Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yanan Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Haijing Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mengfei Yao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ningning Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Bo Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bo Zhang.

Ethics declarations

Conflicts of interest

All authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The original version of this article was revised due to a retrospective Open Access cancellation

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, Y., Cao, Y., Liu, H. et al. Remodelin, an inhibitor of NAT10, could suppress hypoxia-induced or constitutional expression of HIFs in cells. Mol Cell Biochem 472, 19–31 (2020). https://doi.org/10.1007/s11010-020-03776-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-020-03776-w

Keywords

Search

Navigation