miR-885-5p regulates fibrogenic phenotypes in TGF-β1-treated LX-2 cells via targeting NR5A2, with clinical association with MAFLD.

Background

Metabolic-associated fatty liver disease (MAFLD) is a common chronic liver disease worldwide, with liver fibrosis serving as a major determinant of poor prognosis. While miR-885-5p shows dysregulated expression in numerous metabolic and liver disorders, its function in MAFLD has yet to be fully elucidated. The present study seeks to determine the cross-sectional association of miR-885-5p for MAFLD and explore its potential role in regulating fibrogenic phenotypes in hepatic stellate cells via NR5A2 modulation, thus identifying a potential biomarker for further investigation.

Methods

A total of 102 MAFLD patients and 68 healthy controls were recruited. Serum miR-885-5p and NR5A2 were quantified and correlated with clinical indicators. A TGF-β1-induced LX-2 fibrosis model was established; after miR-885-5p inhibitor and si-NR5A2 treatment, CCK-8, oxidative stress, Western blot, and dual-luciferase reporter assays were performed.

Results

Serum miR-885-5p levels were markedly elevated in MAFLD patients, exhibiting considerable potential as cross-sectionally associated diagnostic biomarker for this disease. Dual-luciferase reporter assays verified NR5A2 as a direct downstream target of miR-885-5p. In TGF-β1-stimulated LX-2 cells, miR-885-5p silencing significantly suppressed cell viability, oxidative stress injury, and the expression of fibrotic markers including α-SMA, COL1A1, and TIMP-1. Notably, concurrent NR5A2 knockdown partially abrogated these protective effects.

Conclusions

Serum miR-885-5p is elevated in MAFLD and correlates with disease severity, showing discriminatory potential for metabolic liver involvement. Mechanistically, it promotes HSC activation and fibrogenesis via NR5A2 suppression, representing a candidate therapeutic target.