Ann Hepatol. 2021 Mar-Apr:21:100191.doi: 10.1016/j.aohep.2020.03.003. Epub 2020 Mar 20.

miRNA-338-3p/CAMK IIα signaling pathway prevents acetaminophen-induced acute liver inflammation in vivo



  • 1 Department of Infectious Diseases, The Ninth Hospital of Xi’an, Shaanxi 710054, China.
  • 2 Department of Human Anatomy, Henan Vocational College of Nursing, Anyang 455000, China.
  • 3 Department of Endocrinology, Shaanxi Province TCM Hospital, Xi’an, 710003 Shaanxi, China.
  • 4 Department of Traditional Chinese Medicine, The Hospital of Shaanxi Provincial People, Shaanxi 710068, China.
  • 5 Department of Infectious Diseases, The Hospital of Yan ‘an People, Shaanxi 716000, China. Electronic address:

Free article


Introduction and objectives: N-acetyl-p-aminophenol (APAP)-induced liver injury is a major clinical challenge worldwide. The present study investigated the molecular role of microRNA (miR)-338-3p in the development of APAP-induced acute liver injury.

Materials and methods: B6 mice were treated with an miR-338-3p agomir, antagomir, and intraperitoneally injected with APAP 24h later to induce acute liver injury. Histological analysis was performed to evaluate the degree of liver injury. The gene expression of miR-338-3p and its downstream regulators was measured by reverse transcription-quantitative PCR and western blot. The miR target was validated using a luciferase reporter assay.

Results: The results revealed that miR-338-3p was significantly upregulated following the intraperitoneal administration of APAP. Augmenting miR-338-3p alleviated acute liver injury caused by APAP overdose, while silencing of miR-338-3p exhibited a detrimental effect. Moreover, miR-338-3p inhibited the expression of pro-inflammatory cytokines by preventing the aberrant activation of inflammatory signaling pathways, including the nuclear factor kappa-B (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, calcium/calmodulin-dependent protein kinase IIα (CAMK IIα) was identified as a direct target of miR-338-3p.

Conclusion: The present study demonstrated that miR-338-3p inhibited inflammation in APAP-induced acute liver injury.

Keywords: APAP; CAMK IIα; Liver injury; MAPK; Mir-338-3p; NF-κB.