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

Abstract

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.

Autophagy, Mitophagy and MicroRNA Expression in Chronic Hepatitis C and Autoimmune Hepatitis

“…In the present study, elevated miR-101 was found in CHC samples as compared with AIH cases, which raises concern as miR-101 is an autophagy inhibitor. Suppressed autophagy on the account of miR-101 is reported in breast cancer (targeting RAB5A, STMN1 and ATG4D), HCC (through EZH2) [22,23] and in ischemic liver (via activating mTOR signaling pathway) [41]. Nevertheless, the levels of LC3 and p62 observed in the present study support the activation and not the inhibition of autophagy in CHC.…”

Electroacupuncture Pretreatment Alleviates Cerebral Ischemia-Reperfusion Injury by Regulating Mitophagy via mTOR-ULK1/FUNDC1 Axis in Rats

“…For example, the mTOR signaling is inhibited in liver I/R, 29 and that mTOR activation attenuates inflammatory response and inhibits excessive autophagy in I/R-injured liver. 30,31 Overexpression of cardiac mTOR suppresses the inflammatory response and provides substantial cardioprotection against I/R injury. 32 However, whether mTOR activation is beneficial to cerebral I/R injury remains controversial.…”

Molecular strategies used by hibernators: Potential therapeutic directions for ischemia reperfusion injury and preservation of human donor organs

“…Rosiglitasone, a peroxisome proliferator-activated receptor (PPARγ) agonist was also found to protect against murine ischemic cardiac injury by modifying AMPK activation [57]. Song et al found that AMPK inhibition via the microRNA, miR-101, ameliorated hepatic IR injury and decreased autophagy [58], and Li et al showed hepatocellular protection against IR injury [40].…”