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Review Article
This review examines miRNAs in MASH pathogenesis, lipid metabolism, inflammation, and fibrosis, and their promise as biomarkers and therapeutics. Preclinical results are strong, but delivery, targeting, and standardization remain key hurdles. MiRNA-based diagnostics and therapeutics are precision tools for MASH management.
Metabolic-associated steatohepatitis (MASH) represents a growing global public health challenge. Its complex pathogenesis involves multiple pathological pathways, including lipid metabolism, inflammation, and fibrosis, yet effective specific diagnostic and therapeutic approaches remain elusive. MicroRNAs (miRNAs), as key post-transcriptional regulators, play an important role in the development and progression of MASH. This narrative review examines the molecular mechanisms by which miRNAs regulate lipid accumulation, inflammatory activation, hepatocyte injury, and fibrosis in MASH, while exploring their potential as non-invasive biomarkers for diagnosis and prognosis assessment. Additionally, the article focuses on analyzing the progress of preclinical research and the translational challenges of targeted therapeutic strategies based on miRNA mimics and antagonists, including delivery issues, off-target effects, reproducibility, and long-term safety. Despite encouraging preclinical evidence, major hurdles remain in clinical translation, including the lack of standardized protocols, efficient liver-specific delivery systems, and comprehensive safety data. Addressing these limitations may enable miRNA-based diagnostics and therapeutics to become precision tools for MASH management, though further validation through large-scale prospective studies is required.
The global prevalence of metabolic-associated fatty liver disease (MAFLD) and its inflammatory subtype, metabolic-associated steatohepatitis (MASH), is rapidly increasing, posing a significant public health issue1. As an advanced form of MAFLD, MASH serves as a major precursor to cirrhosis and hepatocellular carcinoma (HCC), and has become one of the primary indications for liver transplantation2,3. The pathological features of MASH are complex, encompassing hepatic steatosis, ballooning degeneration, lobular inflammation, and varying degrees of fibrosis. Its pathogenesis results from t....
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Molecular networks of miRNA regulation in core pathogenesis mechanisms of MASH
Role of miRNAs in hepatic lipid metabolism and insulin resistance
In the pathogenesis of metabolic-associated steatohepatitis (MASH), microRNAs (miRNAs) form a complex molecular network by regulating hepatic lipid metabolism and insulin resistance. Dysregulation of hepatic lipid metabolism represents the initiating and central component of MASH, involving disturbances in lipid synthesis, oxidation, and transport12. Insulin resistance further exacerbates this metabolic imbalance by promoting the release of fr....
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In summary, miRNAs play important roles in MASH pathogenesis by fine-tuning core gene networks involved in lipid metabolism, inflammation, cell death, and fibrosis. Their dynamic expression profiles reflect liver pathology and offer molecular insights into disease heterogeneity.
From a clinical perspective, circulating miRNAs hold promise as non-invasive biomarkers. Their correlation with hepatic pathology supports potential applications in non-invasive diagnosis and stratification of disease .......
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This work was supported by grants from the Qingdao Key Health Discipline Development Program, Key Specialty for Integrated Traditional Chinese and Western Medicine Hepatology (Grant No. 20240357), and the Qingdao Key Health Discipline Development Program, Peak Discipline (Grant No. 20240306).
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