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| Status |
Public on Jun 09, 2023 |
| Title |
N6-methyladenosine-enhanced FZR1 translation contributes to gemcitabine insensitivity in pancreatic cancer via quiescence maintenance [m6A-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Herein, by detecting the global m6A profile in a panel of gemcitabine-sensitive and gemcitabine-insensitive PDAC cells, we identified the key role of hyper-m6A modification of the master G0/G1 regulator Fizzy and Cell Division Cycle 20 Related 1 (FZR1) in regulating gemcitabine sensitivity. Targeting m6A modification of FZR1 improves the gemcitabine treatment response of gemcitabine-insensitive PDAC cells in vitro and in vivo.
Mechanistically, Gem Nuclear Organelle Associated Protein 5 (GEMIN5) was identified as a novel m6A mediator that specifically binds to m6A-modified FZR1 and recruits the eIF3 translation initiation complex to accelerate FZR1 translation. Upregulation of FZR1 maintains the G0/G1 quiescent state and impairs gemcitabine sensitivity of PDAC cells. Further clinical analysis showed that both high levels of FZR1 m6A modification and FZR1 protein indicated a poor response to gemcitabine.
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| Overall design |
m6A-seq data for six PDAC cell lines and GEMIN5 PAR-CLIP-seq of PANC-1
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| Contributor(s) |
Su J, Li R |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Jun 27, 2022 |
| Last update date |
Jun 11, 2023 |
| Contact name |
Rui Li |
| E-mail(s) |
lirui@sysucc.org.cn
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| Organization name |
Sun Yat-sen University Cancer Center
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| Street address |
651 Dongfeng East Road
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| City |
Guangzhou |
| ZIP/Postal code |
510060 |
| Country |
China |
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| Platforms (1) |
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| Samples (12)
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| GSM6267436 |
BXPC-3,GEM-SEN, IP |
| GSM6267437 |
HPC-Y5,GEM-SEN, IP |
| GSM6267438 |
MIA Paca-2,GEM-SEN, IP |
| GSM6267439 |
HPAF-II, GEM-INS, INPUT |
| GSM6267440 |
PANC-1,GEM-INS, INPUT |
| GSM6267441 |
CAPAN-2,GEM-INS, INPUT |
| GSM6267442 |
BXPC-3,GEM-SEN, INPUT |
| GSM6267443 |
HPC-Y5,GEM-SEN, INPUT |
| GSM6267444 |
MIA Paca-2,GEM-SEN, INPUT |
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| This SubSeries is part of SuperSeries: |
| GSE206969 |
N6-methyladenosine modification of FZR1 mRNA promotes gemcitabine resistance in pancreatic cancer |
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| Relations |
| BioProject |
PRJNA853161 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE206968_RAW.tar |
120.0 Kb |
(http)(custom) |
TAR (of NARROWPEAK) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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