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Analysis of miRNA Expression Profiles in High Cholesterol Diet-Induced MASH Progression: Potential Effect of

Tugce Demirel-Yalciner1,2, Bengu Cetinkaya3,4, Kazim Yalcin Arga5

  • 1Department of Biochemistry, Faculty of Medicine, Uskudar University, Istanbul, Turkey.

IUBMB Life
|September 23, 2025
PubMed

Insights

This study identifies key microRNAs (miRNAs) involved in metabolic dysfunction-associated steatohepatitis (MASH) progression in rabbits and assesses the impact of alpha-tocopherol on these miRNA profiles, offering potential diagnostic and therapeutic insights.

Area of Science:

  • Hepatology
  • Molecular Biology
  • Biochemistry

Background:

  • Metabolic dysfunction-associated fatty liver disease (MAFLD) affects a significant portion of the global population.
  • A substantial percentage of MAFLD cases advance to metabolic dysfunction-associated steatohepatitis (MASH), highlighting the disease's growing importance.
  • MicroRNAs (miRNAs) are crucial regulators of cellular processes and are recognized as potential biomarkers in various diseases, including MASH.

Purpose of the Study:

  • To investigate the relationship between MASH and miRNA profiles in a rabbit model of cholesterol-induced MASH.
  • To evaluate the effect of alpha-tocopherol, a known protective agent, on miRNA expression in MASH.
  • To identify novel miRNAs associated with MASH pathogenesis and potential therapeutic targets.

Main Methods:

  • Establishment of a cholesterol-induced MASH model in rabbits.
  • miRNA screening using sequencing to identify known and putative miRNAs.
  • Quantitative reverse transcription PCR (RT-PCR) to determine the levels of specific miRNAs.
  • Target gene prediction to understand the relevance of miRNAs in MASH pathogenesis.

Main Results:

  • Identification of two putative miRNAs (miR-230 and miR-1146) with potential diagnostic and therapeutic significance in MASH.
  • Quantification of five specific miRNAs (miR-122-5p, miR-199-5p, miR-145-5p, miR-27b-3p, miR-34a-5p) and their involvement in MASH pathogenesis.
  • Demonstration of dysregulated miRNA profiles in a high-cholesterol diet-induced MASH model and the influence of alpha-tocopherol.

Conclusions:

  • The study provides novel insights into dysregulated miRNAs in cholesterol-induced MASH in rabbits.
  • Identified miRNAs, particularly miR-230 and miR-1146, may serve as valuable biomarkers for MASH diagnosis and treatment.
  • Alpha-tocopherol demonstrates a modulatory effect on miRNA profiles in MASH, suggesting its therapeutic potential.
Keywords:
MASHhigh cholesterol dietmiRNAsα‐Tocopherol

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