Abstract
Breast cancer is the most prevalent cancer in female patients worldwide. Tissue factor pathway inhibitor 2 (TFPI-2) is identified as an important tumor suppressor in various cancers. Recent studies have shown that TFPI-2 translocates into the nucleus, where it modulates the transcription of the matrix metalloproteinase-2 (MMP-2) gene. However, its biological role and molecular mechanisms in the progression of breast cancer remain unclear. In this study, we identified 5125 differentially expressed genes (DEGs) from RNA sequencing (RNA-seq) in TFPI-2-overexpressing MDA231 cells compared with control cells. Gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) analysis shown that cell cycle, cell differentiation, proteoglycans in cancer, and pathways associated with cancer were highly enriched in downregulated DEGs. Integration of the RNA-seq and ChIP-sequencing (ChIP-seq) data identified 73 genes directly controlled by TFPI-2 in MDA231 cells. Among them, melanocyte inducing transcription factor (MITF) gene expression was repressed by TFPI-2, which was further verified by a luciferase reporter assay and ChIP-quantitative PCR. Our study provides evidence of a novel role of TFPI-2 in human breast cancer involving targeting of the MITF.
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Data Availability
The raw sequence data of ChIP-seq and RNA-seq were obtained in SAR(BioProject ID: PRJNA871386).
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Acknowledgements
We are indebted to Dr. Wei Gu for providing us with MDA231 cells and technical advice.
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This research was supported by funding from the Guangxi Natural Science Foundation (Grant: 2018JJB140005) and Guangxi Bagui Scholars Special Project.
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GW designed the study and final manuscript revisions, and obtained funding. NZ helped GW in designing for the study. GZ performed experiments, and wrote the manuscript. GZ, WY, and BT performed some of the study. CZ, MK, and ZN supervised and directed the study. RC completed the data curation.
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The Ethics Committee at the Affiliated Hospital of Guilin Medical School reviewed and approved this research (YJSLL2021104).
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Wang, G., Zhang, G., Zhu, N. et al. Integrative analyses of RNA-seq and ChIP-seq Reveal MITF as a Target Gene of TFPI-2 in MDA231 Cells. Biochem Genet 61, 1745–1757 (2023). https://doi.org/10.1007/s10528-023-10340-w
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DOI: https://doi.org/10.1007/s10528-023-10340-w