# GNMT and Its Regulatory MicroRNAs as Biomarkers and Therapeutic Targets for Metabolic Dysfunction-Associated Fatty Liver Disease and Hepatocellular Carcinoma

## TL;DR

This paper reviews how GNMT and its regulating microRNAs could serve as biomarkers and treatment targets for liver diseases like HCC and MAFLD.

## Contribution

The paper highlights miR-873-5p and miR-224 as novel post-transcriptional regulators of GNMT in liver diseases.

## Key findings

- GNMT deficiency is strongly linked to hepatocellular carcinoma and MAFLD.
- miR-873-5p and miR-224 directly target GNMT mRNA to suppress its expression in liver diseases.
- Restoring GNMT expression via miRNA inhibition or gene therapy shows therapeutic potential.

## Abstract

Glycine N-methyltransferase (GNMT), a S-adenosylmethionine (SAM)-dependent methyltransferase, is primarily expressed in the liver and plays a key role in regulating liver metabolism and protecting against liver injury. Several studies have shown that deficiency or downregulation of GNMT is strongly associated with the pathogenesis of hepatocellular carcinoma (HCC), highlighting its critical role as a tumor suppressor. Other studies have shown that GNMT is also strongly correlated with the pathogenesis of metabolic dysfunction-associated fatty liver disease (MAFLD). Although many factors regulate GNMT expression, recent studies have identified microRNAs (miRNAs), such as miR-873-5p and miR-224, as key post-transcriptional regulators that directly target GNMT mRNA and suppress its expression in HCC and MAFLD. This review provides an overview of GNMT’s role in liver physiology and how its dysregulation contributes to the progression of HCC and MAFLD, with a focus on the regulation of GNMT by miR-873-5p and miR-224. We also highlight the potential of these two miRNAs as biomarkers and therapeutic targets for HCC and MAFLD, discussing emerging strategies such as antisense-based inhibition, gene therapy, and small-molecule inducers aimed at restoring GNMT expression.