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Upregulation of MHC I Antigen Processing Machinery Gene Expression in Breast Cancer Cells by Trichostatin A

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Abstract

Epigenetic alterations associated with cancer have been shown to facilitate tumorigenesis and promote metastasis. In the study of cancer metastasis, epigenetics has been revealed to play a crucial role in supporting tumour immune evasion. As a result, epigenetic drugs have been identified as potential agents to activate anti-tumour immune responses and reverse tumour immunologically tolerant states. Mounting evidence is showing aberrant expression of MHC class I antigen processing molecules in cancers and their upregulation as a potential indicator for anti-tumour immunity. In this study, we demonstrate that the epigenetic drug Trichostatin A (TSA), a histone deacetylase inhibitor, can restore MHC I antigen presentation machinery (MHC I APM) genes in human breast cancer cells (MCF-7). Treatment with TSA resulted in the upregulation of MHC I, B2M, and PSMB9 in MCF-7 monolayer cells, and MHC I, B2M, PSMB9, PSMB8, TAP1, and TAP2 in MCF-7 spheroid cells. Interestingly, treatment with TSA also increased CD274 expression in these cells and enhanced the invasion ability of the MCF-7 spheroid. This aggressive behaviour was confirmed by increased expression of metastatic-related genes, nNav1.5 and MMP1. In summary, although the restoration of MHC I APM expression was achieved by TSA, the upregulation of metastatic genes and CD274 also enhanced the invasion ability of breast cancer cells. These findings suggest the need for careful consideration when utilizing epigenetic drugs for breast cancer therapy.

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ACKNOWLEDGMENTS

We would like to acknowledge Yayasan Khazanah for the postgraduate financial support and the highest gratitude to the personnel of the Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, for technical assistance.

Funding

Ministry of Higher Education, Malaysia—Fundamental Research Grant Scheme (Reference Code: FRGS/1/2018/ SKK08/USM/03/2) supported this research.

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  1. Institute for Research in Molecular Medicine, Health Campus, Universiti Sains Malaysia, Kubang Kerian, 16150, Kelantan, Malaysia

    A. H. Murtadha, N. A. Sharudin, I. I. M. Azahar & N. F. Mokhtar

  2. Department of Neuroscience, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, 16150, Kelantan, Malaysia

    A. T. Che Has

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  1. A. H. Murtadha
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Murtadha, A.H., Sharudin, N.A., Azahar, I.I. et al. Upregulation of MHC I Antigen Processing Machinery Gene Expression in Breast Cancer Cells by Trichostatin A. Mol Biol 57, 1212–1227 (2023). https://doi.org/10.1134/S0026893324010151

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