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

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing health concern, yet the role of non-coding RNAs (ncRNAs), including microRNAs (miRNAs), in its pathogenesis remains poorly understood. In this pilot study, we aimed to identify significantly expressed miRNAs and ncRNAs and correlate transcriptomic patterns of the findings with previously identified coding gene expression profiles to explore potential regulatory mechanisms in MASLD. Participants were selected from an existing study population. We conducted transcriptomic profiling of miRNAs and other ncRNAs in whole blood samples from African American individuals with MASLD and matched controls (n=4 in each group). miRNA sequencing was performed by Zymo, USA followed by miRNA extraction using Zymo-Seq™ miRNA Library Kit. Differentially expressed RNAs were analyzed using Ingenuity Pathway Analysis (IPA) to identify associated biological pathways. A total of 1,412 miRNAs and 5,423 other ncRNAs were identified in MASLD patients compared to controls. Among them, 35 miRNAs and 28 other ncRNAs exhibited significant differential expressions (fold change cut off 1.5, p < 0.05). miR-206 was upregulated, potentially compensating for insulin resistance, while miR-1343-5p miR-1299, miR-224-5p, and miR-193a-5p were downregulated, connecting impaired lipid metabolism and fibrosis. IPA results identified hepatic fibrosis and cirrhosis pathways enriched with miRNA- other ncRNA interactions. Our findings highlight promising candidates for future biomarker validation and therapeutic targeting. Further large-scale studies are necessary to validate these candidates and elucidate their role in MASLD pathogenesis and ethnic disparities.