Transcriptomic Profiling of MicroRNA and Non-Coding RNA from Whole Blood of African Americans with MASLD.

Area of Science:

• Genomics
• Molecular Biology
• Hepatology

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global health issue.
• The role of non-coding RNAs (ncRNAs), including microRNAs (miRNAs), in MASLD pathogenesis is not well understood.
• African Americans are an under-represented population in MASLD research.

Purpose of the Study:

• To identify differentially expressed miRNAs and ncRNAs in whole blood of African American individuals with MASLD.
• To correlate ncRNA expression patterns with coding gene expression profiles.
• To explore potential ncRNA-mediated regulatory mechanisms in MASLD.

Main Methods:

• Whole-blood transcriptomic profiling of miRNAs and other ncRNAs in a discovery cohort (4 MASLD, 4 controls).
• Validation of differentially expressed ncRNAs using qRT-PCR in a larger cohort (14 MASLD, 16 controls).
• Pathway analysis using Ingenuity Pathway Analysis (IPA) to identify biological associations.

Main Results:

• Identified 1412 miRNAs and 5423 other ncRNAs.
• Found 35 significantly differentially expressed miRNAs and 28 other ncRNAs (FC cutoff 1.5, p < 0.05).
• Validated upregulation of miR-206 and downregulation of miR-185-3p, miR-224-5p, and miR-218-5p, linking them to lipid metabolism and fibrosis via the AMPK/TGF-β pathway.

Conclusions:

• This is the first whole-blood ncRNA transcriptomic study in African American MASLD patients.
• Identified specific miRNAs (miR-206, miR-1343-5p, miR-1299, miR-224-5p, miR-193a-5p) as potential biomarkers for MASLD.
• ncRNAs may play a crucial role in MASLD pathogenesis, warranting further investigation in larger, multi-ethnic cohorts.