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| Status |
Public on Aug 07, 2020 |
| Title |
A3shNT cell transcriptomics |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Altered oncogene expression in cancer cells causes loss of redox homeostasis resulting in oxidative DNA damage, e.g., 8-oxoguanine (8-oxoG), repaired by base excision repair (BER). PARP1 coordinates BER and relies on the upstream 8-oxoguanine-DNA glycosylase (OGG1) to recognise and excise 8-oxoG. Here we hypothesize that OGG1 may represent an attractive target to exploit reactive oxygen species (ROS) elevation in cancer. Although OGG1 depletion is well tolerated in non-transformed cells, we report here that OGG1 depletion obstructs A3 T-cell lymphoblastic acute leukemia growth in vitro and in vivo, validating OGG1 as a potential anti- cancer target. In line with this hypothesis, we show that OGG1 inhibitors (OGG1i) target a wide range of cancer cells, with a favourable therapeutic index compared to non-transformed cells. Mechanistically, OGG1i and shRNA depletion cause lost mitochondrial function leading to S- phase DNA damage, replication stress and proliferation arrest or cell death, representing a novel mechanistic approach to target cancer. This study adds OGG1 to the list of BER factors, e.g., PARP1, as potential targets for cancer treatment. _x000B_
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| Overall design |
A3shNT cells were treated with OGG1 inhibitor TH5487 or DMSO and sequenced 24 hours later
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| Contributor(s) |
Hagey D, Benitez-Buelga C |
| Citation(s) |
33211885 |
| Submission date |
Aug 06, 2020 |
| Last update date |
Dec 15, 2020 |
| Contact name |
Daniel Wesley Hagey |
| E-mail(s) |
daniel.hagey@ki.se
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| Organization name |
Karolinska Institutet
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| Street address |
Nobels vag 3
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| City |
Stockholm |
| ZIP/Postal code |
17177 |
| Country |
Sweden |
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| Platforms (1) |
| GPL21290 |
Illumina HiSeq 3000 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA655614 |
| SRA |
SRP276347 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE155782_A3shNT_COUNT.txt.gz |
377.7 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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