Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Jan 2;24(1):1.
doi: 10.1186/s12935-023-03197-x.

RNA m6A methylation regulators in liver cancer

Qiaoping Xu #  1 , Ning Ren #  2 , Lanqi Ren  2 , Yibei Yang  2 , Junjie Pan  2 , Hongkai Shang  3   4   5   6   7
Affiliations
Review

RNA m6A methylation regulators in liver cancer

Qiaoping Xu et al. Cancer Cell Int. .

Abstract

Liver cancer is one of the most common cancers in the world and a primary cause of cancer-related death. In recent years, despite the great development of diagnostic methods and targeted therapies for liver cancer, the incidence and mortality of liver cancer are still on the rise. As a universal post-transcriptional modification, N6-methyladenosine (m6A) modification accomplishes a dynamic and reversible m6A modification process, which is executed by three types of regulators, methyltransferases (called writers), demethylases (called erasers) and m6A-binding proteins (called readers). Many studies have shown that m6A RNA methylation has an important impact on RNA metabolism, whereas its regulation exception is bound up with the occurrence of human malignant tumors. Aberrant methylation of m6A RNA and the expression of related regulatory factors may be of the essence in the pathogenesis and progression of liver cancer, yet the precise molecular mechanism remains unclear. In this paper, we review the current research situations of m6A methylation in liver cancer. Among the rest, we detail the mechanism by which methyltransferases, demethylases and m6A binding proteins regulate the occurrence and development of liver cancer by modifying mRNA. As well as the potential effect of m6A regulators in hepatocarcinogenesis and progression. New ideas and approaches will be given to the prevention and treatment of liver cancer through the following relevant research results.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interest.

Figures

Fig. 1
Fig. 1
M6A dynamic regulation. Simple model of m6A Dynamic regulation. m6A methylation is regulated by methyltransferase (“Writers”), demethylases (“Erasers”) and m6A-binding proteins (“Readers”). Methyltransferase METTL3/14, WTAP, VIRMA, ZC3H13, RBM15/15B etc. mainly catalyze the modification of mRNA by m6A. Demethylases, including FTO and ALKBH5, are used to demethylate bases modified by m6A. The main function of m6A-binding proteins is to recognize sites modified by m6A, thereby activating downstream regulatory pathways such as RNA degradation and miRNA processing. The m6A site is bound to different readers to accommodate different functions
Fig. 2
Fig. 2
primary contributions of m6A methylases in liver cancer. Major roles of m6A methylases(METTL3、METTL14、WTAP) in the occurrence and development of liver cancer. Increased expression of METTL3: A reduces the stability of SOCS2 mRNA through m6A YTHDF2-dependent pathway, thus promoting the occurrence and development of liver cancer; B promotes the modification of ASPM mRNA and promote the proliferation, migration and invasion of hepatoma cells. Moreover, overexpression of miR-186 significantly inhibited the expression of METTL3, thereby affecting the expression of Wnt/β-catenin pathway-related proteins such as β-catenin, thus promoting the proliferation, migration and invasion of hepatoma cells. METTL14 is a tumor suppressor gene, and its decreased expression may promote hepatocarcinogenesis. The up-regulated expression of WTAP in HCC also indicates poor prognosis and poor patient survival
Fig. 3
Fig. 3
A positive correlation between HBx and ALKBH5 in HBV-HCC tissues. HBx-ALKBH5 may form a positive feedback loop and participate in HBV-induced hepatocarcinogenesis. HBV upregulates the expression of ALKBH5 through the HBx-WDR5-H3K4me3 axis, and ALKBH5 promotes the stabilization of HBx mRNA by reducing m6A fluctuations, thus forming a positive feedback loop
Fig. 4
Fig. 4
Primary contributions of m6A methylases in liver cancer
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Xu J, Yang X, Zhou Q, Zhuang J, Han S. Biological significance of piRNA in liver cancer: a review. Biomarkers. 2020;25(6):436–440. doi: 10.1080/1354750X.2020.1794041. - DOI - PubMed
    1. Ghafouri-Fard S, Honarmand Tamizkar K, Hussen BM, Taheri M. MicroRNA signature in liver cancer. Pathol Res Pract. 2021;219:153369. doi: 10.1016/j.prp.2021.153369. - DOI - PubMed
    1. Ma C, Zhang Q, Greten TF. MDSCs in liver cancer: A critical tumor-promoting player and a potential therapeutic target. Cell Immunol. 2021;361:104295. doi: 10.1016/j.cellimm.2021.104295. - DOI - PMC - PubMed
    1. Chen Y, Miao L, Lin H, Zhuo Z, He J. The role of m6A modification in pediatric cancer. Biochim Biophys Acta Rev Cancer. 2022;1877(2):188691. doi: 10.1016/j.bbcan.2022.188691. - DOI - PubMed
    1. Elsabbagh RA, Rady M, Watzl C, Abou-Aisha K, Gad MZ. Impact of N6-methyladenosine (m(6)A) modification on immunity. Cell Commun Signal. 2022;20(1):140. doi: 10.1186/s12964-022-00939-8. - DOI - PMC - PubMed
-