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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Oct 02, 2020 |
| Title |
Silencing of ZFP36L1 using siRNA |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
ZFP36L1 is a tandem zinc-finger RNA-binding protein that recognizes conserved Adenylate-Uridylate-rich Elements (AREs) located in 3' untranslated regions (UTRs) to mediate RNA decay. We hypothesized that ZFP36L1 is a negative regulator of a post-transcriptional hub involved in the RNA half-life regulation of cancer-related transcripts. Forced expression of ZFP36L1 in cancer cells markedly reduced cell proliferation in vitro and in vivo; whereas silencing of ZFP36L1 enhanced tumor cell growth. To identify direct downstream targets of ZFP36L1, systematic screening using RNA pull-down of wildtype and mutant ZFP36L1 as well as whole transcriptome sequencing of bladder cancer cells ± tet-on ZFP36L1, was performed. A network of 1,410 genes was identified as potential direct targets of ZFP36L1, including HIF1A, CCND1, and E2F1. ZFP36L1 specifically bound to the 3' UTRs of these targets for RNA degradation, thus suppressing their expression. Collectively, our findings reveal an indispensable role of ZFP36L1 as a post-transcriptional safeguard against aberrant hypoxic signaling and abnormal cell cycle progression.
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| Overall design |
mRNA profiles of ZFP36L1 knockdown cells were generated by deep sequencing using BGISEQ-500.
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| Contributor(s) |
Loh X, Sun Q, Ding L, Mayakonda A, Venkatachalam N, Yeo M, Silva TC, Xiao J, Doan NB, Said JW, Ran X, Zhou S, Dakle P, Shyamsunder P, Koh AP, Huang RY, Berman BP, Tan S, Yang H, Lin D, Koeffler HP |
| Citation(s) |
31551365 |
| Submission date |
Aug 22, 2019 |
| Last update date |
Oct 02, 2020 |
| Contact name |
Pushkar Dakle |
| E-mail(s) |
csidpp@gmail.com
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| Organization name |
Cancer Science Institute of Singapore
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| Street address |
14 Medical Drive, #12-01,
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| City |
Singapore |
| ZIP/Postal code |
117599 |
| Country |
Singapore |
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| Platforms (1) |
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| Samples (2) |
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| Relations |
| BioProject |
PRJNA561515 |
| SRA |
SRP219084 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE136180_J82_si.counts.txt.gz |
3.0 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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