Recent Advances in miRNA-Based Therapy for MASLD/MASH and MASH-Associated HCC

Area of Science:

• Hepatology
• Molecular Biology
• Pharmacology

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD), previously NAFLD, affects over 1 billion adults globally.
• MASLD can advance to MASH, cirrhosis, and hepatocellular carcinoma (HCC).
• MicroRNAs (miRNAs) are key regulators in the transition from MASLD to HCC, influencing lipid metabolism, inflammation, and fibrosis.

Purpose of the Study:

• To review the therapeutic potential of miRNA-based interventions for MASLD/MASH and HCC.
• To explore how modulating specific miRNAs can impact liver disease progression.
• To highlight recent preclinical and clinical findings on miRNA-based strategies.

Main Methods:

• Review of recent preclinical and clinical studies on miRNA-based therapies for MASLD/MASH and HCC.
• Analysis of miRNA roles in regulating hepatic gene expression related to liver disease.
• Examination of therapeutic strategies involving miRNA mimics and inhibitors.

Main Results:

• Specific miRNAs can either worsen or alleviate fibrosis and cancer in hepatic cells.
• Preclinical studies show miRNA therapies can reduce liver inflammation, fibrosis, and inhibit tumor growth.
• miRNA modulation holds potential for delaying or preventing HCC development from MASLD/MASH.

Conclusions:

• miRNA-based therapies offer a promising strategy to combat MASLD/MASH and prevent HCC.
• Addressing challenges in delivery, off-target effects, and long-term safety is crucial for clinical translation.
• Further research into miRNA pharmacology is essential for effective treatment development.