Silencing of Long Noncoding RNA AK139328 Attenuates Ischemia/Reperfusion Injury in Mouse Livers

Abstract

Recently, increasing evidences had suggested that long noncoding RNAs (LncRNAs) are involved in a wide range of physiological and pathophysiological processes. Here we determined the LncRNA expression profile using microarray technology in mouse livers after ischemia/reperfusion treatment. Seventy one LncRNAs were upregulated, and 27 LncRNAs were downregulated in ischemia/reperfusion-treated mouse livers. Eleven of the most significantly deregulated LncRNAs were further validated by quantitative PCR assays. Among the upregulated LncRNAs confirmed by quantitative PCR assays, AK139328 exhibited the highest expression level in normal mouse livers. siRNA-mediated knockdown of hepatic AK139328 decreased plasma aminotransferase activities, and reduced necrosis area in the livers with a decrease in caspase-3 activation after ischemia/reperfusion treatment. In ischemia/reperfusion liver, knockdown of AK139328 increased survival signaling proteins including phosphorylated Akt (pAkt), glycogen synthase kinase 3 (pGSK3) and endothelial nitric oxide synthase (peNOS). Furthermore, knockdown of AK139328 also reduced macrophage infitration and inhibited NF-κB activity and inflammatory cytokines expression. In conclusion, these findings revealed that deregulated LncRNAs are involved in liver ischemia/reperfusion injury. Silencing of AK139328 ameliorated ischemia/reperfusion injury in the liver with the activation of Akt signaling pathway and inhibition of NF-κB activity. LncRNA AK139328 might be a novel target for diagnosis and treatment of liver surgery or transplantation.

Knockdown of lncRNA AK139328 alleviates myocardial ischaemia/reperfusion injury in diabetic mice via modulating miR‐204‐3p and inhibiting autophagy

“…Zhao et al demonstrated that lncRNA MALAT1 was involved in myocardial ischaemia‐reperfusion and down‐regulation of MALAT1 contributed to the reduction of cardiomyocyte apoptosis 8. LncRNA AK139328, which has been indicated by Chen et al to be involved in liver I/R injury, is a vital member of lncRNAs 9. However, the mechanism and role of lncRNA AK139328 in MIRI have not been completely investigated.…”

Roles of Non-Coding RNAs in Acute Kidney Injury

“…Emerging evidence shows that lncRNAs are critical regulators of genes involved in a variety of human diseases including AKI [64][65][66]. Recently, microarray assays and RNAsequencing (RNA-seq) methods have been used to evaluate lncRNA expression in animal models of I/R injury or in patients with AKI [64][65][66].…”

“…Recently, microarray assays and RNAsequencing (RNA-seq) methods have been used to evaluate lncRNA expression in animal models of I/R injury or in patients with AKI [64][65][66]. A few lncRNAs are differentially expressed in models of I/R injury in comparison to the control group expression [64][65][66].…”

“…Recently, microarray assays and RNAsequencing (RNA-seq) methods have been used to evaluate lncRNA expression in animal models of I/R injury or in patients with AKI [64][65][66]. A few lncRNAs are differentially expressed in models of I/R injury in comparison to the control group expression [64][65][66]. Of these lncRNAs, the functions of TapSAKI (TrAnscript Predicting Survival in AKI) [64], AK139328 [65] and lncRNA-PRINS (Psoriasis susceptibility-related RNA Gene Induced by Stress) have been well studied ( Table 2) [66].…”

MALAT1 Promotes Cell Apoptosis and Suppresses Cell Proliferation in Testicular Ischemia-Reperfusion Injury by Sponging MiR-214 to Modulate TRPV4 Expression

“…Wu et al showed that lncRNA N1LR reduces neuronal apoptosis and enhances cell proliferation in cerebral IR by targeting Nck1 gene expression [16]. Chen et al demonstrated that silencing of AK139328 inhibits NF-κB and caspase-3 activity with activation of the Akt signaling pathway in hepatic IRI [17]. However, the biological effect of MALAT1 in testicular IRI has not been elucidated.…”