The DOI matches its Crossref record; 48 of the 48 references it cites were found in a registry or an index.
YTHDF2 reduction fuels inflammation and vascular abnormalization in hepatocellular carcinoma
Open accessAbstract
Background: Dynamic N6-methyladenosine (m 6 A) modification was previously identified as a ubiquitous post-transcriptional regulation that affected mRNA homeostasis. However, the m 6 A-related epitranscriptomic alterations and functions remain elusive in human cancer. Here we aim to identify the profile and outcome of m 6 A-methylation in hepatocellular carcinoma (HCC). Results: Using liquid chromatography-tandem mass spectrometry and m 6 A-immunoprecipitation in combination with high-throughput sequencing, we determined the m 6 A-mRNA levels in human HCC. Human HCC exhibited a characteristic gain of m 6 A modification in tandem with an increase of mRNA expression, owing to YTH domain family 2 (YTHDF2) reduction. The latter predicted poor classification and prognosis of HCC patients, and highly correlated with HCC m 6 A landscape. YTHDF2 silenced in human HCC cells or ablated in mouse hepatocytes provoked inflammation, vascular reconstruction and metastatic progression. Mechanistically, YTHDF2 processed the decay of m 6 A-containing interleukin 11 (IL11) and serpin family E member 2 (SERPINE2) mRNAs, which were responsible for the inflammation-mediated malignancy and disruption of vascular normalization. Reciprocally, YTHDF2 transcription succumbed to hypoxia-inducible factor-2α (HIF-2α). Administration of a HIF-2α antagonist (PT2385) restored YTHDF2-programed epigenetic machinery and repressed liver cancer. Conclusion: Our results have characterized the m 6 A-mRNA landscape in human HCC and revealed YTHDF2 as a molecular ‘rheostat’ in epitranscriptome and cancer progression.
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1 retracted
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Self-citationRetractedTopology of the human and mouse m6A RNA methylomes revealed by m6A-seq
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N6-methyladenosine-dependent regulation of messenger RNA stability
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Self-citationDynamic RNA Modifications in Gene Expression Regulation
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Self-citationRecognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation
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FTO Plays an Oncogenic Role in Acute Myeloid Leukemia as a N 6 -Methyladenosine RNA Demethylase
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Cited by
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
m6A-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
Chen, Y., Zhao, Y., Chen, J., Peng, C., Zhang, Y., Tong, R., Cheng, Q., Yang, B., Feng, X., Lu, Y., et al. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01239-w · Cited by 284
Lipid nanoparticle topology regulates endosomal escape and delivery of RNA to the cytoplasm
Zheng, L., Bandara, S. R., Tan, Z., & Leal, C. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2301067120 · Cited by 259
Reading the m6A-encoded epitranscriptomic information in development and diseases
Chen, Y., Zhou, Z., Chen, Y., & Chen, D. (2024) · Cell & Bioscience · doi:10.1186/s13578-024-01293-7 · Cited by 24
Metadata
- Authors
- Hou, J., Zhang, H., Liu, J., Zhao, Z., Wang, J., Lu, Z., Hu, B., Zhou, J., Zhao, Z., Feng, M., Zhang, H., Shen, B., Huang, X., Sun, B., He, C., & Xia, Q.
- Venue
- Molecular Cancer
- Published
- 2019-11-18
- Volume
- 18
- Issue
- 1
- Pages
- 163-163
- ISSN
- 1476-4598 (ISSN-L)
- OpenAlex
- W2984672214
- Cited by
- 361
- References
- 48
- FWCI
- 14.18
- Type
- journal article
- Language
- en
- Open access
- gold
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- Hou, J., Zhang, H., Liu, J., Zhao, Z., Wang, J., Lu, Z., Hu, B., Zhou, J., Zhao, Z., Feng, M., Zhang, H., Shen, B., Huang, X., Sun, B., He, C., & Xia, Q. (2019). YTHDF2 reduction fuels inflammation and vascular abnormalization in hepatocellular carcinoma. Molecular Cancer. https://doi.org/10.1186/s12943-019-1082-3
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