Abstract
Triple-negative breast cancer (TNBC) is a heterogeneous and aggressive disease with poor prognosis. Acetylation modifications affect a great number of biological processes of malignant tumors. The current study aims at revealing the role of acetylation-related mechanism in TNBC progression. Methyltransferase like-3 (METTL3) was found to be downregulated in TNBC cells via quantitative polymerase chain reaction (qPCR) and western blot analyses. Co-Immunoprecipitation (Co-IP) and GST pulldown assays revealed the interaction between acetyl-CoA acetyltransferase 1 (ACAT1) and METTL3. Through further immunoprecipitation (IP) assay, we determined that ACAT1 stabilizes METTL3 protein via inhibiting the degradation of ubiquitin-proteasome. Functionally, ACAT1 inhibits TNBC cell migration and invasion. Moreover, nuclear receptor subfamily 2 group F member 6 (NR2F6) regulates ACAT1 expression at transcriptional level. Finally, we demonstrated that NR2F6/ACAT/METTL3 axis suppresses the migration and invasion of TNBC cells via METTL3. In conclusion, NR2F6 transcriptionally activates ACAT1 and promotes the suppressive effects of ACAT1-mediated METTL3 acetylation on TNBC cell migration and invasion.
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The data that support the findings of this study are available from the corresponding author upon reasonable request.
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GZ, RY, and HZ designed the research study. GZ, RY, HZ, YK, and HH performed the research and completed the figures. MJ and YH provided help and advice on the experiments. YY wrote the manuscript.
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Zhang, G., Huang, R., Zhao, H. et al. ACAT1-mediated METTL3 acetylation inhibits cell migration and invasion in triple negative breast cancer. Genes Immun 24, 99–107 (2023). https://doi.org/10.1038/s41435-023-00202-1
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DOI: https://doi.org/10.1038/s41435-023-00202-1