The DOI matches its Crossref record; 54 of the 54 references it cites were found in a registry or an index.
m6A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade
Open accessAbstract
Melanoma is one of the most deadly and therapy-resistant cancers. Here we show that N 6-methyladenosine (m 6 A) mRNA demethylation by fat mass and obesity-associated protein (FTO) increases melanoma growth and decreases response to anti-PD-1 blockade immunotherapy. FTO level is increased in human melanoma and enhances melanoma tumorigenesis in mice. FTO is induced by metabolic starvation stress through the autophagy and NF-κB pathway. Knockdown of FTO increases m 6 A methylation in the critical protumorigenic melanoma cell-intrinsic genes including PD-1 (PDCD1), CXCR4, and SOX10, leading to increased RNA decay through the m 6 A reader YTHDF2. Knockdown of FTO sensitizes melanoma cells to interferon gamma (IFNγ) and sensitizes melanoma to anti-PD-1 treatment in mice, depending on adaptive immunity. Our findings demonstrate a crucial role of FTO as an m 6 A demethylase in promoting melanoma tumorigenesis and anti-PD-1 resistance, and suggest that the combination of FTO inhibition with anti-PD-1 blockade may reduce the resistance to immunotherapy in melanoma.
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PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
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N6-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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N6-Methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO
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The role of m6A modification in the biological functions and diseases
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Role of RNA modifications in cancer
Barbieri, I., & Kouzarides, T. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-020-0253-2 · Cited by 1,312
The potential role of RNA N6-methyladenosine in Cancer progression
Wang, T., Kong, S., Tao, M., & Ju, S. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01204-7 · Cited by 1,013
m 6 A RNA methylation: from mechanisms to therapeutic potential
He, P. C., & He, C. (2021) · The EMBO Journal · doi:10.15252/embj.2020105977 · Cited by 786
Self-citationm6A-binding proteins: the emerging crucial performers in epigenetics
Zhao, Y., Shi, Y., Shen, H., & Xie, W. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00872-8 · Cited by 316
Metadata
- Authors
- Yang, S., Wei, J., Cui, Y.-H., Park, G., Shah, P., Deng, Y., Aplin, A. E., Lu, Z., Hwang, S., He, C., & He, Y.-Y.
- Venue
- Nature Communications
- Published
- 2019-06-25
- Volume
- 10
- Issue
- 1
- Pages
- 2782-2782
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2953467762
- Cited by
- 743
- References
- 54
- FWCI
- 28.86
- Type
- journal article
- Language
- en
- Open access
- gold
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- Yang, S., Wei, J., Cui, Y.-H., Park, G., Shah, P., Deng, Y., Aplin, A. E., Lu, Z., Hwang, S., He, C., & He, Y.-Y. (2019). m6A mRNA demethylase FTO regulates melanoma tumorigenicity and response to anti-PD-1 blockade. Nature Communications. https://doi.org/10.1038/s41467-019-10669-0
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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.
