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Status |
Public on Mar 31, 2022 |
Title |
Reduction N6AMT1-mediated 6mA DNA modification promotes tumor progression [MeDIP-seq] |
Organism |
Homo sapiens |
Experiment type |
Methylation profiling by high throughput sequencing
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Summary |
Background: DNA N6-methyladenosine (6mA) as a novel epigenetic signaling modification in humans and has been implicated in progression and tumorigenesis of several cancers. However, the function and mechanisms of 6mA in breast cancer (BC), the most common cancer among women, are unclear. Methods: The clinical role of 6mA was investigated by immunohistochemical (IHC) staining and Kaplan-Meier analysis of BC and their normal tissues. 6mA immunoprecipitation (IP) sequencing, mRNA sequencing and bioinformatics analysis were used to screen and validate the direct targets of 6mA. Results: Decreases in N6AMT1 correlated with the extent of 6mA in BC tissues and predicted a worse overall survival of BC patients. Knockdown N6AMT1 markedly reduced 6mA in DNA and promoted the proliferation and migration of BC in vivo and in vitro, whereas overexpression of N6AMT1 had the opposite effect, indicating N6AMT1 is a functional methyltransferase for DNA 6mA and relates with gene transcription. Critical negative regulators of the cell cycle, such as RB1, P21, REST and TP53 were identified as targets of N6AMT1 in BC. Conclusion: These results suggest N6AMT1 enhances DNA 6mA levels to repress tumor progression via transcriptional regulation of cell cycle inhibitors.
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Overall design |
Global 6mA profiles of MDA-MB-453 cells by transfected with siRNAs for N6AMT1 (n=2) or Controls (n=2).
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Contributor(s) |
Chen J, Zhuang Y, Wang P, Ning J, Liu W, Huang Y, Lin X, Peng L, Zhang D |
Citation(s) |
35256595 |
Submission date |
Feb 10, 2021 |
Last update date |
Apr 01, 2022 |
Contact name |
Ping Wang |
E-mail(s) |
pingwangwp@gmail.com
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Organization name |
Tianjin Medical University
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Street address |
No22.Qixiangtai Rd.,Heping Dist
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City |
Tianjin |
ZIP/Postal code |
300000 |
Country |
China |
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Platforms (1) |
GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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Samples (6)
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This SubSeries is part of SuperSeries: |
GSE166582 |
Reduction N6AMT1-mediated 6mA DNA modification promotes tumor progression |
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Relations |
BioProject |
PRJNA701301 |
SRA |
SRP305734 |