Abstract
Malignant liver cancer is characterized by rapid tumour progression and a high mortality rate, whereas the molecular mechanisms underlying liver cancer initiation and progression are still poorly understood. The dynamic and reversible RNA modifications have crucial functions in gene expression regulation by modulating RNA processing and mRNA translation. Emerging evidence has revealed that alterations in RNA modifications facilitate the selective translation of oncogenic transcripts and promote the diverse tumorigenic processes of liver cancer. In this Review, we first highlight the current progress on the functions and mechanisms underlying RNA modifications in the regulation of mRNA translation and then summarize the exciting discoveries on aberrant RNA modification-mediated mRNA translation in the regulation of tumour initiation, metastasis, metabolism, tumour microenvironment, and drug and radiotherapy resistance in liver cancer. Finally, we discuss the diagnostic and therapeutic potentials of targeting RNA modifications and mRNA translation for the clinical management of liver cancer.
Key points
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Epigenetic changes, including DNA methylation, histone modifications and RNA modifications, have critical roles in liver cancer initiation and progression.
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The dynamic and reversible RNA modifications have crucial functions in the regulation of RNA processing and mRNA translation.
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Aberrant modifications on mRNAs, tRNAs and ribosomal RNAs regulate the translation of oncogenic transcripts and promote diverse tumorigenic aspects of liver cancer.
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Targeting aberrant RNA modification-mediated mRNA translation could be promising for the development of effective diagnostic and therapeutic strategies for liver cancer.
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Acknowledgements
The authors sincerely thank S. Peng, X. Zeng, H. Han, Z. Dai, S. Guo, H. Liu, S. Zheng, H. Guan, Y. Hou and S. Li for their helpful discussions. S.L. is supported by National Key Research and Development Program (2022YFA1105300 and 2022YFE0138700), National Natural Science Foundation of China (82325036 and 81974435), Distinguished Young Scholars grant from Natural Science Foundation of Guangdong (2019B151502011), and Fundamental Research Funds for the Central Universities, Sun Yat-sen University (23ykzy004). M.K. is supported by the Key Program of National Natural Science Foundation of China (82130083), National Science Fund for Distinguished Young Scholars (81825013), and the Key Research and Development Plan of Guangzhou City (202206080016).
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Lin, S., Kuang, M. RNA modification-mediated mRNA translation regulation in liver cancer: mechanisms and clinical perspectives. Nat Rev Gastroenterol Hepatol 21, 267–281 (2024). https://doi.org/10.1038/s41575-023-00884-y
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DOI: https://doi.org/10.1038/s41575-023-00884-y
