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| Status |
Public on Apr 26, 2024 |
| Title |
DRAIC mediates hnRNPA2B1 stability and m6A-modified IGF1R instability to inhibit tumor progression |
| Organism |
Homo sapiens |
| Experiment type |
Other
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| Summary |
Both N6-methyladenosine (m6A) mediates RNA fates and ubiquitin mediates protein fates play an important role in either physiology or pathology including cancer, yet how long noncoding RNAs (lncRNAs) are involved in a link of molecular fate between m6A and ubiquitin remains unknown. Here, we reveal a role for a lncRNA Downregulated RNA in Cancer (DRAIC) to suppress tumor growth and metastasis in clear cell Renal Carcinoma (ccRCC). Mechanistically, DRAIC physically interacts with heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1) and enhances its protein stability by blocking E3 ligase F-box protein 11 (FBXO11)-mediated ubiquitin and proteasome-dependent degradation. Subsequently, hnRNPA2B1 destabilizes m6A modified-type 1 insulin-like growth factor receptor (IGF1R) to lead to inhibition of ccRCC progression. Moreover, four m6A modification sites of IGF1R are identified and results in its mRNA degradation. Collectively, our findings reveal that DRAIC/hnRNPA2B1 axis regulates IGF1R mRNA expression in an m6A-dependent manner and highlights an important mechanism of IGF1R fate. These findings shed light on DRAIC/hnRNPA2B1/FBXO11/IGF1R axis as potential therapeutic targets in ccRCC and build a link of molecular fate between m6A-modified RNA and ubiquitin-modified protein.
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| Overall design |
RIP assay was performed using m6A antibody in 786-0 cells and the enriched RNA was sequenced with input sample
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| Contributor(s) |
Wen Y, Yang X, Li Y, Zhao X, Duan L, Chenge S, Peng B, Zhua X, Chang X, Zhang C, Cheng T, Wang H, Zhang Y, Gao S |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| Submission date |
Mar 26, 2024 |
| Last update date |
Apr 26, 2024 |
| Contact name |
Shan Gao |
| E-mail(s) |
gaos@sibet.ac.cn
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| Organization name |
Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences
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| Street address |
Keling Road 88
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| City |
Suzhou |
| ZIP/Postal code |
215163 |
| Country |
China |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA1092059 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE262500_RAW.tar |
567.8 Mb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
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