The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.
m6A mRNA methylation regulates AKT activity to promote the proliferation and tumorigenicity of endometrial cancer
Open accessAbstract
N6-methyladenosine (m6A) messenger RNA methylation is a gene regulatory mechanism affecting cell differentiation and proliferation in development and cancer. To study the roles of m6A mRNA methylation in cell proliferation and tumorigenicity, we investigated human endometrial cancer in which a hotspot R298P mutation is present in a key component of the methyltransferase complex (METTL14). We found that about 70% of endometrial tumours exhibit reductions in m6A methylation that are probably due to either this METTL14 mutation or reduced expression of METTL3, another component of the methyltransferase complex. These changes lead to increased proliferation and tumorigenicity of endometrial cancer cells, likely through activation of the AKT pathway. Reductions in m6A methylation lead to decreased expression of the negative AKT regulator PHLPP2 and increased expression of the positive AKT regulator mTORC2. Together, these results reveal reduced m6A mRNA methylation as an oncogenic mechanism in endometrial cancer and identify m6A methylation as a regulator of AKT signalling. Liu et al. show that reduced m6A mRNA methylation in endometrial cancer is oncogenic. Mechanistically, the AKT pathway is activated in these tumours due to altered expression of AKT regulators carrying m6A on their transcripts.
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“Sequencing studies have found that the METTL14 subunit of the core m 6 A methyltransferase complex is frequently mutated in endometrial tumors 36 , but the relevance of these mutations and of m 6 A mRNA methylation to the disease has not yet been established.”
InfluentialN6-methyladenosine-dependent regulation of messenger RNA stability
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Self-citationComprehensive Analysis of mRNA Methylation Reveals Enrichment in 3′ UTRs and near Stop Codons
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Cited by
Role of RNA modifications in cancer
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The role of m6A RNA methylation in cancer
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Anti-tumour immunity controlled through mRNA m6A methylation and YTHDF1 in dendritic cells
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Metadata
- Authors
- Liu, J., Eckert, M. A., Harada, B. T., Liu, S.-M., Lu, Z., Yu, K., Tienda, S. M., Chryplewicz, A., Zhu, A. C., Yang, Y., Huang, J.-T., Chen, S.-M., Xu, Z.-G., Leng, X.-H., Yu, X.-C., Cao, J., Zhang, Z., Liu, J., Lengyel, E., & He, C.
- Venue
- Nature Cell Biology
- Published
- 2018-08-27
- Volume
- 20
- Issue
- 9
- Pages
- 1074-1083
- ISSN
- 1465-7392 (ISSN-L)
- 1476-4679
- OpenAlex
- W2886253007
- Cited by
- 778
- References
- 22
- FWCI
- 29.66
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Liu, J., Eckert, M. A., Harada, B. T., Liu, S.-M., Lu, Z., Yu, K., Tienda, S. M., Chryplewicz, A., Zhu, A. C., Yang, Y., Huang, J.-T., Chen, S.-M., Xu, Z.-G., Leng, X.-H., Yu, X.-C., Cao, J., Zhang, Z., Liu, J., Lengyel, E., & He, C. (2018). m6A mRNA methylation regulates AKT activity to promote the proliferation and tumorigenicity of endometrial cancer. Nature Cell Biology. https://doi.org/10.1038/s41556-018-0174-4
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
