MicroRNA Regulation in Liver Disease and Regeneration

MicroRNAs are endogenous, small non-coding RNAs that regulate gene expression by promoting degradation or inhibiting translation of specific messenger RNAs. In the healthy liver, precise microRNA expression maintains lipid and glucose metabolism, bile acid homeostasis and quiescence of hepatic stellate cells. Perturbations in microRNA networks contribute to the pathogenesis of acute liver injury, chronic inflammation, fibrosis and cirrhosis by modulating cytokine signalling, cell survival pathways and extracellular matrix production. During liver regeneration, following partial hepatectomy or toxic insults, distinct microRNAs orchestrate the proliferative and remodelling phases by targeting cell-cycle regulators and growth factor axes. Recent technological advances in high-throughput sequencing and in vivo delivery of microRNA mimics or inhibitors have elucidated key regulatory circuits—such as those centred on miR-122, miR-21 and the let-7 family—as crucial determinants of hepatic repair and fibrogenesis. Owing to their stability in blood and capacity to control multiple targets, microRNAs are under active investigation both as non-invasive biomarkers for staging liver disease and as therapeutic agents to enhance regeneration or attenuate fibrosis on a global scale.

Research from Nature Portfolio

Recent studies have demonstrated the therapeutic potential of synthetic microRNA mimics in models of acute liver failure. Administration of a miR-125b-5p mimic in murine models of paracetamol-induced and FAS-mediated toxicity reduced hepatocellular death, attenuated liver injury markers and improved survival. Mechanistic analysis revealed that miR-125b-5p directly targets the mRNA of Keap1, leading to activation of Nrf2-driven antioxidant pathways and enhanced cytoprotection. These findings position miR-125b-5p mimic as a promising broad-spectrum intervention to limit acute hepatic injury and support clinical translation of microRNA-based therapies.

MicroRNA Regulation in Liver Disease and Regeneration publication trend

The graph below shows the total number of articles in microrna regulation in liver disease and regeneration across all publications each year (not limited to Nature Index journals).

Technical terms

microRNA: A small non-coding RNA molecule that regulates gene expression post-transcriptionally.

Hepatocyte: The main functional cell type in the liver, responsible for metabolism, detoxification and protein synthesis.

Fibrosis: The accumulation of extracellular matrix proteins, leading to scarring and impaired organ function.

Cirrhosis: Advanced stage of liver fibrosis characterised by nodular regeneration and compromised hepatic architecture.

Regeneration: The process by which the liver restores its mass and function after injury or surgical resection.

References

1. The Role of Non-Coding RNAs in Liver Disease, Injury, and Regeneration. Cells (2023).
2. From Inflammation to Oncogenesis: Tracing Serum DCLK1 and miRNA Signatures in Chronic Liver Diseases. International Journal of Molecular Sciences (2024).
3. MicroRNA-125b-5p mimic inhibits acute liver failure. Nature Communications (2016).