2022  1,200
2021  1,540
2020  1,374
2019  1,023
2018  0,932
2017  0,977
2016  0,799
2015  0,662
2014  0,740
2013  0,739
2012  0,637
2011  0,658
2010  0,654
2009  0,570
2008  0,849
2007  0,805
2006  0,330
2005  0,435
2004  0,623
2003  0,567
2002  0,641
2001  0,490
2000  0,477
1999  0,762
1998  0,785
1997  0,507
1996  0,518
1995  0,502
Vol 57(2023) N 6 p. 1212-1227; DOI 10.1134/S0026893324010151 Full Text

A.H. Murtadha1, N.A. Sharudin1, I.I.M. Azahar1, A.T. Che Has2, N.F. Mokhtar1*

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

1Institute for Research in Molecular Medicine, Health Campus, Universiti Sains Malaysia, Kubang Kerian, Kelantan, 16150 Malaysia
2Department of Neuroscience, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, 16150 Malaysia

Received - 2023-02-22; Revised - 2023-05-17; Accepted - 2023-05-19

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 MHCIAPM 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.

MHC I, TSA, breast cancer, invasion, metastasis, epigenetic, PD-L1, nNav1.5, MMP1