MicroRNA-122 Dynamics in Hepatic Carcinogenesis

MicroRNA-122 (miR-122) is a liver-enriched non-coding RNA that orchestrates key hepatocyte functions, including lipid metabolism, differentiation and cell cycle control. In hepatic carcinogenesis, miR-122 is frequently downregulated or lost, unleashing oncogenic programmes that drive proliferation, metabolic reprogramming, invasion and therapy resistance. Its expression is governed by transcription factors such as HNF4α and FXR and is modulated by inflammatory cytokines, while its downstream targets—among them IGF1R, PKM2, RhoA and AKT3—mediate changes in epithelial-mesenchymal transition, glycolysis and survival signalling. The cumulative disruption of the miR-122 network accelerates tumour growth and dissemination. Restoring miR-122 function or correcting its regulatory axis has emerged as a promising avenue for reinstating tumour suppression and enhancing treatment efficacy in liver cancer.

Research from Nature Portfolio

Recent integrative profiling of miRNA and mRNA expression in paired tumorous and non-tumorous liver tissues identified miR-122 as one of six miRNAs significantly downregulated in hepatocellular carcinoma. Upregulated targets of miR-122 were enriched in pathways governing DNA replication, transcription and nucleotide metabolism, while downregulated targets clustered in metabolic and immune system processes. This coordinated regulatory landscape underscores miR-122’s central role in suppressing aberrant cell proliferation and metabolic dysregulation and highlights its potential as a therapeutic target to rectify oncogenic networks in the liver.

MicroRNA-122 Dynamics in Hepatic Carcinogenesis publication trend

The graph below shows the total number of articles in microrna-122 dynamics in hepatic carcinogenesis across all publications each year (not limited to Nature Index journals).

Technical terms

microRNA-122 (miR-122): a liver-specific small non-coding RNA that regulates gene expression post-transcriptionally.

Hepatocarcinogenesis: the process by which normal hepatic cells transform into malignant liver cancer cells.

Transforming growth factor-β1 (TGFβ1): a cytokine that regulates inflammation, cell proliferation and extracellular matrix remodelling.

Bone morphogenetic protein-6 (BMP6): a member of the TGFβ superfamily involved in iron metabolism and inflammatory signalling in the liver.

Epithelial-mesenchymal transition (EMT): a cellular programme in which epithelial cells lose polarity and gain migratory, invasive properties.

Mesenchymal-epithelial transition (MET): the reverse of EMT, restoring epithelial characteristics and tissue cohesion.

Insulin-like growth factor-binding protein 4 (IGFBP4): a ligand-binding protein that modulates IGF availability and influences tumour cell invasion.

References

1. MicroRNA-122 in human cancers: from mechanistic to clinical perspectives. Cancer Cell International (2023).
2. Activation of IGFBP4 via unconventional mechanism of miRNA attenuates metastasis of intrahepatic cholangiocarcinoma. Hepatology International (2023).
3. Differential Modulation of miR-122 Transcription by TGFβ1/BMP6: Implications for Nonresolving Inflammation and Hepatocarcinogenesis. Cells (2023).
4. MicroRNA-122 Inhibits Tumorigenic Properties of Hepatocellular Carcinoma Cells and Sensitizes These Cells to Sorafenib*. Journal of Biological Chemistry (2009).
5. MiR-122 Inhibits Cell Proliferation and Tumorigenesis of Breast Cancer by Targeting IGF1R. PLOS ONE (2012).
6. miR-122 Targets Pyruvate Kinase M2 and Affects Metabolism of Hepatocellular Carcinoma. PLOS ONE (2014).
7. MicroRNA-122 Triggers Mesenchymal-Epithelial Transition and Suppresses Hepatocellular Carcinoma Cell Motility and Invasion by Targeting RhoA. PLOS ONE (2014).
8. Decreased Expression of Hepatocyte Nuclear Factor 4α (Hnf4α)/MicroRNA-122 (miR-122) Axis in Hepatitis B Virus-associated Hepatocellular Carcinoma Enhances Potential Oncogenic GALNT10 Protein Activity*. Journal of Biological Chemistry (2014).
9. MiR-122 Reverses the Doxorubicin-Resistance in Hepatocellular Carcinoma Cells through Regulating the Tumor Metabolism. PLOS ONE (2016).
10. miR-122 Regulates Tumorigenesis in Hepatocellular Carcinoma by Targeting AKT3. PLOS ONE (2013).
11. Upregulation of microRNA-122 by farnesoid X receptor suppresses the growth of hepatocellular carcinoma cells. Molecular Cancer (2015).
12. Differentially Expressed miRNAs in Hepatocellular Carcinoma Target Genes in the Genetic Information Processing and Metabolism Pathways. Scientific Reports (2016).