2. Academic Validation
  3. Hepatic microRNA-320 restrains ferroptosis to mitigate acute-on-chronic alcohol-induced liver injury

Hepatic microRNA-320 restrains ferroptosis to mitigate acute-on-chronic alcohol-induced liver injury

  • Biochim Biophys Acta Mol Basis Dis. 2025 Apr;1871(4):167748. doi: 10.1016/j.bbadis.2025.167748.
Wenjun Li 1,  Li Liu 1,  Shengying Qian 2,  Yingfen Chen 2,  Ru Ya 2,  Ningning Ma 2,  Yawen Hao 2,  Shujun Ge 1,  Xiaoxiao Zhang 1,  Liu Yang 3,  Yong He 4
Affiliations

Affiliations

  • 1 School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, China.
  • 2 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, Beijing, China.
  • 3 Department of Pharmacology, School of Basic Medical Science, Nanjing Medical University, Nanjing, China. Electronic address: yangliu_24072@njmu.edu.cn.
  • 4 School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing, China; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai, China; University of Chinese Academy of Sciences, Beijing, China. Electronic address: heyong@simm.ac.cn.
PMID: 40015214 DOI: 10.1016/j.bbadis.2025.167748
Abstract

Alcohol-associated Liver Disease (ALD) is one of the major chronic liver diseases worldwide and has high mortality and high incidence rate. microRNA-320 (miR-320), a highly conserved and widely expressed miRNA, has been reported to be involved in lipid metabolism; however, whether miR-320 affects the progression of ALD remains unclear. In this study, we demonstrated that hepatic miR-320 was significantly downregulated in chronic-plus-binge alcohol-fed mice. Interestingly, such downregulation might accelerate ALD progression as evidenced that hepatocyte-specific miR-320 deficient mice displayed higher susceptibility to acute-on-chronic alcohol feeding-induced steatosis and inflammation. Moreover, restoration of hepatic miR-320 ameliorated acute-on-chronic alcohol-induced hepatocyte damage and steatosis. Mechanistically, miR-320 inhibited alcohol-induced Ferroptosis by targeting Transferrin Receptor 1 (TFRC) to suppress iron accumulation. Moreover, silencing of Tfrc in hepatocytes attenuated ethanol-induced iron accumulation, thus inhibiting Ferroptosis and ultimately mitigating ALD. Taken together, these findings suggest that miR-320 plays an important role in limiting ALD progression via inhibiting Ferroptosis, providing a therapeutic target for the treatment of ALD.

Keywords

ALD; Ferroptosis; TFRC; miR-320.

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