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Pharmacological inhibition of HDAC1/3-interacting proteins induced morphological changes, and hindered the cell proliferation and migration of hepatocellular carcinoma cells

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Abstract

Liver diseases are particularly severe health problems, but the options available for preventing and treating them remain limited. Accumulating evidence has shown that there is altered expression of individual histone deacetylase (HDAC) family members in hepatocellular carcinoma cells. In a previous study, we have identified a set of proteins which interact with histone deacetylase 1 and 3 (HDAC1/3) in hepatocellular carcinoma cell lines HepG2 by proteomic approach. This study was designed to investigate the therapeutic potential and expression of HDAC1/3-interacting genes in a human hepatocellular carcinoma cell line (HepG2). Pharmacological and transcriptional inhibition of HDAC1/3 resulted in the suppression of cancer cell proliferation, change of cell morphology, and downregulation of HDAC1/3 genes in HepG2 cells. The pharmacological inhibition also resulted in inhibition of liver cancer cell migration by wound scratch assay. Taken together, the results from this study show that the upregulation of HDAC1/3 in hepatocellular carcinoma resulted in the overexpression of CNOT1, PFDN2/6, and HMG20B, and that these genes could serve as novel molecular targets in liver cancer.

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All data generated or analyzed during this study are included in this published article.

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Acknowledgements

The authors thank the Deanship of Scientific Research and RSSU at King Saud University for the technical support. The authors also acknowledge Najla bin Shwish, Mary Grace Vigilla, and Rhodanne Lambarte for their assistance and contributions to this report, and the Molecular and Cell Biology Laboratory, a core research facility of the King Saud University College of Dentistry, in collaboration with the Prince Naif bin AbdulAziz Health Research Center, where part of this study was performed.

Funding

This study was funded by the Deanship of Scientific Research, King Saud University, through the Vice Deanship of Scientific Research Chairs. The funding body had no role in the design, collection, analysis, and interpretation of data, or writing of the manuscript.

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Authors and Affiliations

  1. Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia

    Nouf Al-yhya & Rafa Sharaf Almeer

  2. Bio-products Research Chair, Department of Zoology, College of Science, King Saud University, P.O. Box 2455, Riyadh, 11451, Saudi Arabia

    Muhammad Farooq Khan & Mohammad Ahmed Wadaan

  3. King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, King Abdulaziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia

    Mana M Alshehri

  4. Research Center, King Fahad Medical City, P.O.BOX:59046, Riyadh, 1152, Saudi Arabia

    Mohammed S. Aldughaim

Authors
  1. Nouf Al-yhya
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Contributions

Conceptualization: M.F.K., R.S.A., and M.A.W. Methodology: M.F.K., N.A.Y., and M.M.A. Resources: M.F.K., M.S.A., and M.A.W. Data curation: N.A.Y., M.F.K., M.M.A., and M.S.A. Writing—original draft preparation: M.F.K., N.A.Y., M.M.A. Writing—review and editing: M.F.K., M.M.A., M.S.A., R.S.A., and M.A.W. Supervision: M.F.K. Funding acquisition: M.F.K. and M.A.W. All the authors have read and agreed to the published version of the manuscript.

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Correspondence to Muhammad Farooq Khan.

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Al-yhya, N., Khan, M.F., Almeer, R.S. et al. Pharmacological inhibition of HDAC1/3-interacting proteins induced morphological changes, and hindered the cell proliferation and migration of hepatocellular carcinoma cells. Environ Sci Pollut Res 28, 49000–49013 (2021). https://doi.org/10.1007/s11356-021-13668-1

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