Liver cancer is a common cancer worldwide. Although the etiological factors of liver carcinogenesis are well defined, the underlying molecular mechanisms remain largely elusive. Epigenetic deregulations, such as aberrant DNA methylation and histone modifications, play a critical role in liver carcinogenesis. Analogous to DNA and core histone proteins, reversible chemical modifications on mRNA have recently been recognized as important regulatory mechanisms to control gene expression. N6-methyladenosine (m6A) is the most prevalent internal mRNA modification in mammalian cells. m6A modification is important for controlling many cellular and biological processes. Deregulation of m6A modification has been recently implicated in human carcinogenesis, including liver cancer. In this review, we summarize the recent findings on m6A regulation and its biological impacts in normal and cancer cells. We will focus on the deregulation of m6A modification and m6A regulators in liver diseases and liver cancers. We will highlight the clinical relevance of m6A deregulation in liver cancer. We will also discuss the potential of exploiting m6A modification for cancer diagnosis and therapeutics.
Keywords: Epi-transcriptome; Hepatocellular carcinoma; N6-methyladenosine; RNA epigenetics.
Conflict of interest statement
The authors declare that they have no competing interests.
RNA N6-methyladenosine methyltransferase-like 3 promotes liver cancer progression through YTHDF2-dependent posttranscriptional silencing of SOCS2.Hepatology. 2018 Jun;67(6):2254-2270. doi: 10.1002/hep.29683. Epub 2018 Apr 19. Hepatology. 2018. PMID: 29171881
Epigenetic N6-methyladenosine modification of RNA and DNA regulates cancer.Cancer Biol Med. 2020 Feb 15;17(1):9-19. doi: 10.20892/j.issn.2095-3941.2019.0347. Cancer Biol Med. 2020. PMID: 32296573 Free PMC article. Review.
The potential role of RNA N6-methyladenosine in Cancer progression.Mol Cancer. 2020 May 12;19(1):88. doi: 10.1186/s12943-020-01204-7. Mol Cancer. 2020. PMID: 32398132 Free PMC article. Review.
Functions of N6-methyladenosine and its role in cancer.Mol Cancer. 2019 Dec 4;18(1):176. doi: 10.1186/s12943-019-1109-9. Mol Cancer. 2019. PMID: 31801551 Free PMC article. Review.
Emerging function of N6-methyladenosine in cancer.Oncol Lett. 2018 Nov;16(5):5519-5524. doi: 10.3892/ol.2018.9395. Epub 2018 Sep 4. Oncol Lett. 2018. PMID: 30344705 Free PMC article. Review.