The Role of RNA Methyltransferase METTL3 in Hepatocellular Carcinoma: Results and Perspectives

Abstract

Hepatocellular carcinoma (HCC) is the 6th most prevalent cancer and the 4th leading cause of cancer-related death worldwide. Mechanisms explaining the carcinogenesis of HCC are not clear yet. In recent years, rapid development of N⁶-methyladenosine (m6A) modification provides a fresh approach to disclosing this mystery. As the most prevalent mRNA modification in eukaryotes, m6A modification is capable to post-transcriptionally affect RNA splicing, stability, and translation, thus participating in a variety of biological and pathological processes including cell proliferation, apoptosis, tumor invasion and metastasis. METTL3 has been recognized as a pivotal methyltransferase and essential to the performance of m6A modification. METTL3 can regulate RNA expression in a m6A-dependent manner and contribute to the carcinogenesis, tumor progression, and drug resistance of HCC. In the present review, we are going to make a clear summary of the known roles of METTL3 in HCC, and explicitly narrate the potential mechanisms for these roles.

Keywords: Hepatocellular carcinoma; METTL3; RNA modification; drug-resistance; m6A.

FIGURE 1

Dynamic and reversible regulation of m6A modification by regulators including “writers,” “readers,” and “erasers.” M6A “writers” serve as methyltransferases, such as WTAP and METTL3/14. M6A “readers” help recognize and bind to m6A-modified transcripts, like YTHDF1/2 and YTHDC1. M6A “erasers” have the ability for demethylation, such as FTO and ALKBH5.

FIGURE 2

Roles of METTL3 as a methyltransferase in HCC. Different targets of METTL3 are associated with diverse signaling pathways and biological processes, which contribute to the different influences of METTL3 on HCC.