Wang et al. 2021 (PRJNA622261)
General Details
| Title | N1-methyladenosine methylations in tRNA drive liver tumorigenesis by PPARδ-mediated cholesterol synthesis |
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| Organism | |
| Number of Samples | 2 |
| Release Date | 2020/03/31 00:00 |
| Sequencing Types | |
| Protocol Details |
Study Links
| GWIPS-viz | Trips-Viz |
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Repository Details
| SRA | SRP254791 |
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| ENA | SRP254791 |
| GEO | GSE147840 |
| BioProject | PRJNA622261 |
Publication
| Title | |
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| Authors | Wang Y,Wang J,Li X,Xiong X,Wang J,Zhou Z,Zhu X,Gu Y,Dominissini D,He L,Tian Y,Yi C,Fan Z |
| Journal | Nature communications |
| Publication Date | 2021 Nov 2 |
| Abstract | Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers and is characterized by high recurrence and heterogeneity, yet its mechanism is not well understood. Here we show that N 1 -methyladenosine methylation (m 1 A) in tRNA is remarkably elevated in hepatocellular carcinoma (HCC) patient tumour tissues. Moreover, m 1 A methylation signals are increased in liver cancer stem cells (CSCs) and are negatively correlated with HCC patient survival. TRMT6 and TRMT61A, forming m 1 A methyltransferase complex, are highly expressed in advanced HCC tumours and are negatively correlated with HCC survival. TRMT6/TRMT61A-mediated m 1 A methylation is required for liver tumourigenesis. Mechanistically, TRMT6/TRMT61A elevates the m 1 A methylation in a subset of tRNA to increase PPARδ translation, which in turn triggers cholesterol synthesis to activate Hedgehog signaling, eventually driving self-renewal of liver CSCs and tumourigenesis. Finally, we identify a potent inhibitor against TRMT6/TRMT61A complex that exerts effective therapeutic effect on liver cancer. © 2021. The Author(s). |
| PMC | PMC8563902 |
| PMID | 34728628 |
| DOI |
| Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) | ||
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| SRR11459635 | PRJNA622261 | Homo sapiens | Normal PLC cells | Ribo-Seq |  |
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| SRR11459636 | PRJNA622261 | Homo sapiens | Ribo-Seq | |
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| Run Accession | Study Accession | Scientific Name | Cell Line | Library Type | Treatment | GWIPS-viz | Trips-Viz | Reads | BAM | BigWig (F) | BigWig (R) |
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