The DOI matches its Crossref record; 69 of the 69 references it cites were found in a registry or an index.
N1-methyladenosine methylation in tRNA drives liver tumourigenesis by regulating cholesterol metabolism
Open accessAbstract
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 N1-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.
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Sorafenib in Advanced Hepatocellular Carcinoma
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Genome-Wide Analysis in Vivo of Translation with Nucleotide Resolution Using Ribosome Profiling
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Dynamic RNA Modifications in Gene Expression Regulation
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Tumour heterogeneity and cancer cell plasticity
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Cited by
Cancer stem cells: advances in knowledge and implications for cancer therapy
Chu, X., Tian, W., Ning, J., Xiao, G., Zhou, Y., Wang, Z., Zhai, Z., Tanzhu, G., Yang, J., & Zhou, R. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01851-y · Cited by 553
Metadata
- 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.
- Venue
- Nature Communications
- Published
- 2021-11-02
- Volume
- 12
- Issue
- 1
- Pages
- 6314-6314
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W3208877024
- Cited by
- 265
- References
- 69
- FWCI
- 10.73
- Type
- journal article
- Language
- en
- Open access
- gold
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- 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. (2021). N1-methyladenosine methylation in tRNA drives liver tumourigenesis by regulating cholesterol metabolism. Nature Communications. https://doi.org/10.1038/s41467-021-26718-6
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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