Mir-140-5p Alleviates Mouse Liver Ischemia/Reperfusion Injury By Targeting Capn1

Ischemia/reperfusion (I/R)-induced liver injury remains a primary concern in liver transplantation and hepatectomy. Previous studies have indicated that microRNAs (miRs) are involved in multiple pathophysiological processes, including liver I/R. miR-140-5p reportedly inhibits inflammatory responses and apoptosis in several diseases; however, the role of miR-140-5p in liver I/R remains unknown. The present study aimed to investigate the potential role and mechanism of miR-140-5p on liver I/R injury. Mouse liver I/R and mouse AML12 cell hypoxia/reoxygenation (H/R) models were established. miR-140-5p mimics, inhibitor or agonists were used to overexpress or inhibit miR-140-5p in vitro and in vivo. Reverse transcription-quantitative polymerase chain reaction was used to detect miR-140-5p expression. Liver and cell injury were evaluated using several biochemical assays. The association between miR-140-5p and calpain-1 (CAPN1) was confirmed using a dual-luciferase reporter assay. The results revealed that miR-140-5p expression was decreased in the mouse model of liver I/R injury and AML12 cells subjected to H/R, while overexpressed miR-140-5p reduced liver injury in vivo and cell injury in vitro. In addition, CAPN1 was determined to be a target of miR-140-5p; overexpressed CAPN1 abrogated the effect of miR-140-5p on H/R-induced cell injury. The present study indicated that miR-140-5p protected against liver I/R by targeting CAPN1, which may provide a novel therapeutic target for liver I/R injury.