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N6-methyladenosine RNA methylation in liver diseases: from mechanism to treatment

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Abstract

Epigenetic modification occurring in RNA has become the hotspot of the field. N6-methyladenosine (m6A) methylation is the most abundant RNA internal modification mainly occurring at the consensus motif DR (m6A) CH (D = A/G/U, R = A/G, H = A/C/U) in the 3’-UTR particularly the region near stop codons. The life cycle of m6A methylation includes “writers,” “erasers,” and “readers”, which are responsible for the addition, removal, and recognition of m6A, respectively. m6A modification has been reported changing RNA secondary structure or modulating the stability, localization, transport, and translation of mRNAs to play crucial roles in various physiological and pathological conditions. Liver, as the largest metabolic and digestive organ, modulates vital physiological functions, and its dysfunction gives rise to the occurrence of various diseases. Despite the advanced intervening measures, mortality due to liver diseases is continuously high. Recent studies have explored the roles of m6A RNA methylation in the pathogenesis of liver diseases, providing new insights for studying the molecular mechanism of liver diseases. In the review, we extensively summarize the life cycle of m6A methylation, as well as its function and relevant mechanisms in liver fibrosis (LF), nonalcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), hepatitis virus infection, and hepatocellular carcinoma (HCC), and eventually we explore the potential of m6A as a treatment option for these liver diseases.

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Acknowledgements

The study was funded by National Natural Science Foundation of China (No. 81820108005, 82270551, 81900502), National Key R&D Program of China (No. 2020YFA0710803 and 2017YFA0105704) and Key R&D Program of Shaanxi (No. 2021ZDLSF02-07 and 2022ZDLSF03-03). The Fig. 2 was drawn by Figdraw website (www.figdraw.com).

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  1. Lan Yang and Siyuan Tian have contributed equally to this work.

Authors and Affiliations

  1. Department of Plastic and Aesthetic Surgery, Nanfang Hospital of Southern Medical University, Guangzhou, 510515, Guangdong Province, China

    Lan Yang

  2. State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Air Force Military Medical University, 127 Changle West Road, Xi’an, 710032, People’s Republic of China

    Siyuan Tian, Xiaohong Zheng, Miao Zhang, Xinmin Zhou, Yulong Shang & Ying Han

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  1. Lan Yang
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LY, ST, XZ, and MZ contributed to collection of references and manuscript writing. XZ contributed to manuscript revisions. YH and YS contributed to determining the subject and manuscript revisions. All authors contributed to the article and approved the submission.

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Correspondence to Lan Yang, Yulong Shang or Ying Han.

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Yang, L., Tian, S., Zheng, X. et al. N6-methyladenosine RNA methylation in liver diseases: from mechanism to treatment. J Gastroenterol 58, 718–733 (2023). https://doi.org/10.1007/s00535-023-02008-4

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