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| Status |
Public on Jul 09, 2023 |
| Title |
N6-methyladenosine modification is essential for prostate cancer cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
Other
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| Summary |
N6-methyladenosine (m6A) modification of messenger RNAs (mRNAs) is a pivotal mechanism controlling mRNA fate in cells. RNA m6A modification is regulated by the functional balance between methyltransferases and demethylases. Here we demonstrated that FTO-IT1 enhancer RNA (eRNA), a long non-coding RNA (lncRNA) transcribed from the last intron of FTO gene is significantly upregulated in CRPC and aggressive tumors compared to primary tumors. FTO-IT1 knockout by CRISPR/Cas9 almost completely blocks growth and G1-S cell cycle transition of both androgen-sensitive and castration-resistant prostate cancer cells. Meanwhile, the mRNA m6A was dramatically increased in FTO-IT knockout PCa cells and we identified FTO-IT1 as a binding partner of FTO. From m6A-seq, we unexpectedly found hypermethylated m6A associated with upregulated levels of the mRNAs for p53 signaling pathway genes in 22Rv1 prostate cancer cells. Mechanistic study showed that FTO-IT1 recruits FTO to the P53 target mRNA to promote their m6A demethylation, which leads to their degradation.
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| |
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| Overall design |
MeRIP-seq was performed on both wild-type and FTO KO prostate cancer cells
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| |
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| Contributor(s) |
Wei J, Cui X, Zhang J, He C, Huang H |
| Citation(s) |
37478845 |
| |
| Submission date |
Nov 23, 2021 |
| Last update date |
Oct 08, 2023 |
| Contact name |
Xiaolong Cui |
| E-mail(s) |
xiaolong.cui@northwestern.edu
|
| Organization name |
Northwestern University
|
| Department |
Department of Preventive Medicine
|
| Street address |
680 N Lake Shore Drive
|
| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60611 |
| Country |
USA |
| |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA783056 |
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