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Updated: Aug 6, 2026
Mouse Model of Metabolic Dysfunction-Associated Steatotic Liver Disease with Fibrosis
Published on: July 18, 2025
MiR-339-5p promotes hepatic steatosis and inflammation in MASLD by targeting SORT1
Bing Zhang1, Yinge Zhang2, Xuejun Xie3
1Department of Gastroenterology, Affiliated Hospital of Chifeng College, Chifeng, China.
Objective:
This study investigated the clinical significance of serum miR-339-5p in MASLD and explored its molecular mechanisms in hepatic steatosis and inflammation.
Methods:
87 MASLD patients (Np-MASLD, n = 51; MASH-F, n = 36) were enrolled. Serum miR-339-5p was quantified and correlated with clinical indices. In vitro studies used FFA-treated HepG2 cells to assess miR-339-5p and SORT1 effects on lipid accumulation, inflammation.
Results:
Serum miR-339-5p was significantly elevated in MASLD, correlating positively with disease severity, and served as an independent risk factor for MASH-F progression. In HepG2 cells, miR-339-5p overexpression exacerbated FFA-induced lipid accumulation and IL-6/TNF-α secretion, whereas its inhibition exerted protective effects. SORT1 was validated as a direct target of miR-339-5p and was downregulated in MASLD. miR-339-5p suppressed AMPK phosphorylation and promoted NF-κB activation by targeting SORT1.
Conclusion:
Elevated miR-339-5p promotes hepatocyte lipid accumulation and inflammation in MASLD, potentially by targeting SORT1.
Insights
Serum miR-339-5p is elevated in metabolic dysfunction-associated steatotic liver disease (MASLD), promoting liver fat accumulation and inflammation. This microRNA may serve as a biomarker and therapeutic target for MASLD progression.
Area of Science:
- Biochemistry
- Molecular Biology
- Hepatology
Background:
- Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing health concern.
- Understanding the molecular mechanisms driving MASLD, including hepatic steatosis and inflammation, is crucial.
- MicroRNAs (miRNAs) are increasingly recognized for their roles in liver disease pathogenesis.
Purpose of the Study:
- To investigate the clinical significance of serum miR-339-5p in MASLD.
- To explore the molecular mechanisms of miR-339-5p in hepatic steatosis and inflammation.
- To identify potential diagnostic or prognostic biomarkers for MASLD.
Main Methods:
- Serum miR-339-5p levels were quantified in 87 MASLD patients and correlated with clinical indices.
- In vitro studies utilized free fatty acid (FFA)-treated HepG2 cells.
- The effects of miR-339-5p and its target SORT1 on lipid accumulation and inflammation were assessed.
Main Results:
- Serum miR-339-5p was significantly elevated in MASLD patients and correlated with disease severity.
- miR-339-5p overexpression exacerbated FFA-induced lipid accumulation and inflammatory cytokine secretion (IL-6, TNF-α) in HepG2 cells.
- SORT1 was identified as a direct target of miR-339-5p, and its downregulation in MASLD was observed; miR-339-5p targeted SORT1 to suppress AMPK phosphorylation and activate NF-κB.
Conclusions:
- Elevated serum miR-339-5p is a potential biomarker for MASLD severity and MASH-F progression.
- miR-339-5p promotes hepatocyte lipid accumulation and inflammation in MASLD, partly by targeting SORT1.
- Targeting miR-339-5p or modulating SORT1 may offer therapeutic strategies for MASLD.