MiR-122-5p serves as a novel
biomarker for
drug-induced liver injury (DILI), but its function in DILI remains unclear. The present study, therefore, explored the function and potential mechanism of miR-122-5p in DILI. Sprague-Dawley (SD) rats were treated with miR-122-5p
antagomir, and then DILI was induced in the rats by
acetaminophen (
APAP). To determine the effect of miR-122-5p on DILI in vivo, liver injury was examined by HE staining and TUNEL assays, and the levels of serum ALT and AST were determined using an automated clinical chemistry analyzer. To further reveal the mechanism of miR-122-5p in DILI, THLE-2 (normal liver cell line) cells were transfected with miR-122-5p mimic and inhibitor, NDRG3, and siNDRG3, and then injured by
APAP. The relationship between miR-122-5p and NDRG3 was determined by TargetScan,
luciferase reporter assay, and Western blot. The viability and apoptosis of THLE-2 cells were detected by
CCK-8 and flow cytometry, respectively. The levels of
mRNA and
protein in vivo and in vitro were measured by qRT-PCR and Western blot, respectively.
APAP induced liver injury and increased the levels of ALT, AST, and miR-122-5p in DILI rats. However, these effects of
APAP were attenuated by miR-122-5p
antagomir. MiR-122-5p negatively regulated NDRG3 expression.
APAP decreased cell viability, apoptosis resistance, and Bcl-w and Bcl-2 levels whereas increased Bax level in THLE-2 cells. However, these effects of
APAP on THLE-2 cells were promoted by miR-122-5p up-regulation but inhibited by miR-122-5p knockdown. MiR-122-5p knockdown protects against
APAP-mediated liver injury through up-regulating NDRG3.