MicroRNA-101 inhibits autophagy to alleviate liver ischemia/reperfusion injury via regulating the mTOR signaling pathway

Liver ischemia/reperfusion injury (LIRI) is a common complication of liver surgery, and affects liver function post-transplantation. However, the precise mechanism underlying LIRI has not yet been completely elucidated. Previous studies have demonstrated the involvement of a number of microRNAs (miRNAs/miRs) in liver pathophysiology. The objective of the present study was to determine the potential function and mechanism of miR-101-mediated regulation of autophagy in LIRI. Compared with the sham-treated group, a significant decrease in miR-101 and mechanistic target of rapamycin (mTOR) expression levels following ischemia/reperfusion (IR) were observed, along with an increased number of autophagosomes (P<0.001). The exogenous overexpression of miR-101 has been demonstrated to inhibit autophagy during the LIRI response and the levels of mTOR and phosphorylated (p)-mTOR expression are correspondingly elevated. However, compared with the miR-NC group, miR-101 silencing was associated with reduced mTOR and p-mTOR levels and increased autophagy, as indicated by the gradual increase in the levels of the microtubule-associated protein 1 light II (LC3II). The peak levels of LC3II were observed 12 h subsequent to reperfusion, which coincided with the lowest levels of miR-101. In addition, inhibition of autophagy by 3-methyladenine significant enhanced the protective effect of miR-101 against LIRI, compared with the IR group (P<0.001). Altogether, miR-101 attenuates LIRI by inhibiting autophagy via activating the mTOR pathway.