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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Mar 20, 2023 |
| Title |
Opioid receptor signaling suppresses leukemia by inducing TET-dependent DNA demethylation [5hmC-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Acute myeloid leukemia (AML) is a group of heterogeneous diseases with high malignancy. The ten-eleven translocation (TET) mediated DNA demethylation was known to be critically associated with AML pathogenesis. Through chemical compound screening, we found an opioid receptor agonist, namely loperamide hydrochloride (OPA1), most significantly suppressed AML cell viability. The potential therapeutic effects of opioid receptor agonists, especially OPA1, were then verified in AML cells in vitro, and AML mouse models carrying t(11q23) and t(8;21) in vivo. OPA1-induced activation of OPRM1 enhanced the transcription of TET2, increased DNA 5-hydroxymethylcytosine (5hmC) modification, and in turn, activated NFκB signaling. Notably, AML with TET2 mutations or chemotherapy resistance were sensitive to OPA1. Our results unveiled the previously unappreciated OPRM1-TET2-5hmC-TRAF2 regulatory axis in AML, and highlighted the therapeutic potential of opioid agonists, particularly OPA1, a FDA-approved antidiarrheal drug, in treating AML, especially TET2 mutated AML and chemotherapy-resistant AML, which were known to have poor prognosis.
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| Overall design |
Examination of 5hmC modifications in THP-1 cells treated with OPA1 or DMSO.
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| Contributor(s) |
Zhao H, Lu J |
| Citation missing |
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| Submission date |
Mar 25, 2020 |
| Last update date |
Mar 20, 2023 |
| Contact name |
Jun Lu |
| E-mail(s) |
lujun4726@zju.edu.cn
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| Phone |
18258826247
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| Organization name |
Zhejiang University
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| Street address |
866 Yuhangtang Road
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| City |
Hangzhou |
| State/province |
Zhejiang |
| ZIP/Postal code |
3100058 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (4)
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| This SubSeries is part of SuperSeries: |
| GSE147511 |
Opioid agonists as potential AML therapy |
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| Relations |
| BioProject |
PRJNA615095 |
| SRA |
SRP253988 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE147509_All_sample_peaks.xlsx |
2.0 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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