The emerging roles of N6-methyladenosine (m6A) deregulation in liver carcinogenesis

Chun-Ming Wong,Mengnuo Chen

doi:10.1186/s12943-020-01172-y

Chun-Ming Wong, Mengnuo Chen

Open Access

https://doi.org/10.1186/s12943-020-01172-y

Copy DOI

Abstract

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.

Highlights

Liver cancer is a common malignancy and lethal disease globally
RNA m6A modification is emerging as a new layer of post-transcriptional regulation of gene expression
The implications of m6A modification in human carcinogenesis have been demonstrated in different cancer types, including Hepatocellular Carcinoma (HCC)

Summary

Introduction

Liver cancer is a common malignancy and lethal disease globally. the risk factors for liver carcinogenesis are well defined, the underlying molecular mechanisms remain ambiguous. Deregulation of epigenetic regulators is frequently reported in human cancers, including HCC. The above mentioned m6A “reader” proteins have diversified functions and are involved in regulating almost every step of RNA metabolism, including the stability, translation, and splicing of m6A-containing transcripts (Fig. 1).

Results

Conclusion