This review aims to synthesize current evidence on the role of microRNAs (miRNAs) as key epigenetic regulators in metabolic dysfunction-associated steatotic liver disease (MASLD) and to evaluate their emerging potential as non-invasive biomarkers and therapeutic targets. Dysregulated miRNAs—including miR-122, miR-34a, and miR-21—have been shown to modulate central pathways in MASLD, such as lipid metabolism, insulin signaling, inflammation, and fibrogenesis. Circulating miRNAs, particularly those encapsulated within extracellular vesicles like exosomes, show promise as non-invasive biomarkers for diagnosis and staging, although discordance between hepatic and serum expression remains a challenge. Combinatorial miRNA panels improve diagnostic accuracy and prognostic stratification. Therapeutically, strategies using antagomirs and mimics have demonstrated potential in preclinical models, yet issues of delivery efficiency and off-target effects hinder clinical translation. miRNAs play a multifaceted role in MASLD pathogenesis and represent promising tools for biomarker development and targeted therapy. Future efforts should focus on standardizing detection methods, validating miRNA panels in large cohorts, and advancing delivery systems to realize the clinical potential of miRNA-based interventions in MASLD.
Zeng et al. (Mon,) studied this question.