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| Status |
Public on Jul 27, 2019 |
| Title |
Genome-wide identification of transcripts associated with KIAA1429 by RIP-seq |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
N6-methyladenosine (m6A) modification, as the most abundant internal methylation of eukaryotic RNA transcripts, is critically implicated in RNA processing, decay, transport and translation. Here we showed that KIAA1429, the largest known component in the m6A methyltransferase complex, was considerably upregulated in hepatocellular carcinoma (HCC) tissues. High expression of KIAA1429 was significantly associated with the malignant clinical features and the poor prognosis of HCC patients. Silencing KIAA1429 suppressed the cell proliferation and metastasis in vitro and in vivo. Integrated MeRIP-seq, RIP-seq and RNA-seq data identified GATA3 as the direct downstream target of KIAA1429-mediated m6A modification. KIAA1429 knockdown markedly impaired the m6A levels of GATA3 mRNA and increased the expression of GATA3. Mechanistically, KIAA1429 induced the m6A methylation on 3’ UTR of GATA3 pre-mRNA, leading to the separation of RNA-binding protein HuR and the degradation of GATA3 pre-mRNA, which was followed by the downregulation of GATA3. Strikingly, a long noncoding RNA (lncRNA) GATA3-AS, transcribed from the antisense strand of GATA3 gene, functioned as a cis-acting element for the preferential interaction of KIAA1429 with GATA3 pre-mRNA. Accordingly, we found that the tumor growth and metastasis driven by KIAA1429 or GATA3-AS were mediated by GATA3. Patients with low KIAA1429 and high GATA3 expressions showed greatly better poor overall survival and disease-free survival. In conclusion, our study proposed a complex KIAA1429-GATA3 regulatory model based on m6A modification and provided insights into the epi-transcriptomic dysregulation in hepatocarcinogenesis and metastasis.
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| Overall design |
To identify mRNA species bound by KIAA1429, we performed the RIP-seq to immunoprecipitate endogenous mRNAs associated with the KIAA1429 and sequenced the retrieved RNA.
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| Contributor(s) |
Lan T, Li H, Zhang D, Liu H |
| Citation(s) |
31856849 |
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| Submission date |
Jul 26, 2019 |
| Last update date |
Dec 26, 2019 |
| Contact name |
Tian Lan |
| E-mail(s) |
[email protected]
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| Organization name |
West China Hospital
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| Department |
Department of Liver Surgery & Liver Transplantation
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| Lab |
Laboratory of Liver Surgery
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| Street address |
No. 37 of Guoxue Lane
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| City |
Chengdu |
| State/province |
Sichuan |
| ZIP/Postal code |
610041 |
| Country |
China |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA556906 |
| SRA |
SRP216543 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE134978_RAW.tar |
4.3 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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