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Status |
Public on Dec 31, 2023 |
Title |
Alteration of DNMT1/DNMT3A by eribulin elicits global DNA methylation changes with potential therapeutic implications for triple-negative breast cancer |
Organism |
Homo sapiens |
Experiment type |
Methylation profiling by genome tiling array
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Summary |
Triple-negative breast cancer (TNBC) is an aggressive disease subtype with limited treatment options. Eribulin is a chemotherapeutic approved for the treatment of advanced breast cancer that has been shown to elicit epigenetic changes. We investigated the effect of eribulin treatment on genome-scale DNA methylation patterns in TNBC cells. Following repeated treatment, The results showed that eribulin-induced changes in DNA methylation patterns evident in persister cells. Eribulin also affected the binding of transcription factors to genomic ZEB1 binding sites and regulated several cellular pathways, including ERBB and VEGF signaling and cell adhesion. Eribulin also altered the expression of epigenetic modifiers including DNMT1, TET1, and DNMT3A/B in persister cells. Data from primary human TNBC tumors supported these findings: DNMT1 and DNMT3A levels were altered by eribulin treatment in human primary TNBC tumors. Our results suggest that eribulin modulates DNA methylation patterns in TNBC cells by altering the expression of epigenetic modifiers. These findings have clinical implications for using eribulin as a therapeutic agent.
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Overall design |
Bisulfite converted DNA from the untreated, eribulin and paclitaxel treated MDA-MB-231 cell lines were hybridised to the Illumina Infinium Human MethylationEPIC Beadchip.
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Contributor(s) |
Bagheri M, Lee MK |
Citation(s) |
38356412 |
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Submission date |
Jun 13, 2023 |
Last update date |
May 04, 2024 |
Contact name |
Min Kyung Lee |
E-mail(s) |
min.kyung.lee.gr@dartmouth.edu, sarahminkyunglee@gmail.com
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Organization name |
Dartmouth College
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Street address |
1 Medical Center Dr
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City |
Lebanon |
State/province |
NH |
ZIP/Postal code |
03756 |
Country |
USA |
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Platforms (1) |
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Samples (11)
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GSM7476152 |
bisulfite treated genomic DNA from MDA-MB-231 cells treated once with eribulin [MDA_ERI1_Rep1] |
GSM7476153 |
bisulfite treated genomic DNA from MDA-MB-231 cells treated once with eribulin [MDA_ERI1_Rep2] |
GSM7476154 |
bisulfite treated genomic DNA from MDA-MB-231 cells treated twice with eribulin [MDA_ERI2_Rep1] |
GSM7476155 |
bisulfite treated genomic DNA from MDA-MB-231 cells treated twice with eribulin [MDA_ERI2_Rep2] |
GSM7476156 |
bisulfite treated genomic DNA from MDA-MB-231 cells untreated [MDA_P_Rep1] |
GSM7476157 |
bisulfite treated genomic DNA from MDA-MB-231 cells untreated [MDA_P_Rep2] |
GSM7476158 |
bisulfite treated genomic DNA from MDA-MB-231 cells untreated [MDA_P_Rep3] |
GSM7476159 |
bisulfite treated genomic DNA from MDA-MB-231 cells treated once with paclitaxel [MDA_PAC1_Rep1] |
GSM7476160 |
bisulfite treated genomic DNA from MDA-MB-231 cells treated once with paclitaxel [MDA_PAC1_Rep2] |
GSM7476161 |
bisulfite treated genomic DNA from MDA-MB-231 cells treated twice with paclitaxel [MDA_PAC2_Rep1] |
GSM7476162 |
bisulfite treated genomic DNA from MDA-MB-231 cells treated twice with paclitaxel [MDA_PAC2_Rep2] |
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Relations |
BioProject |
PRJNA983438 |