MiR‐27a‐5p regulates apoptosis of liver ischemia‐reperfusion injury in mice by targeting Bach1

Abstract

Ischemia-reperfusion (I/R) injury causes cellular dysfunction and a series of immune or apoptotic reactions. Bach1 is a mammalian transcription factor that represses Hmox1, which encodes heme oxygenase-1 (HO-1) that can degrade heme into free iron, carbon monoxide, and biliverdin, to play an important role in antioxidant, anti-inflammatory, and antiapoptotic activities. MicroRNAs (miRNAs) can be found in a variety of eukaryotic cells and viruses, a class of noncoding small RNAs that are encoded by endogenous genes. The aims of this study were to determine whether miR-27a-5p targets Bach1 and regulates cellular death; the dual-luciferase reporter assay was used to detect this and the results showed that miR-27a-5p significantly decreased the luciferase activity of the Bach1 3'-untranslated region. MiR-27a-5p was increased in mice during hepatic I/R and Bach1 was decreased. By transfecting the AML12 cells with the mimic, inhibitor miR-27a-5p in hypoxia/reoxygenation (H/R) models showed that overexpression of miR-27a-5p decreased Bach1 messenger RNA, upregulated HO-1 expression, and promoted antiapoptotic Bcl-2 and downregulated proapoptotic caspase-3 gene expression. In contrast, the miR-27a-5p inhibitor yielded the opposite results. Meanwhile, transfection with Bach1 small interference RNA obviously upregulated the protein levels of HO-1 and resulted in an increase in Bcl-2 and a decrease in caspase-3 protein levels. Thus, we can conclude that miR-27a-5p is relevant to liver I/R injury and overexpression of miR-27a-5p may alleviate apoptosis in H/R injury by targeting Bach1 in vitro.

The Role of Mitochondria in Liver Ischemia-Reperfusion Injury: From Aspects of Mitochondrial Oxidative Stress, Mitochondrial Fission, Mitochondrial Membrane Permeable Transport Pore Formation, Mitophagy, and Mitochondria-Related Protective Measures

“…As another transcription factor, Bach1 encodes HO-1 to degrade serotonin into the free body, carbon monoxide, and bilirubin. Furthermore, microRNA-27a-5p upregulates HO-1 by targeting Bach1 to increase the expression of Bcl-2 and decrease the expression of Caspase-3 [ 94 ]. In addition, HO-1 protects the liver by limiting the inflammatory response and enhancing the antiapoptotic pathways; thus, the use of Zinc protoporphyrin (ZnPP) which inhibits the expression of HO-1 could increase the content of cytochrome C and Bax [ 95 ], and interferon regulatory factor 9 (IRF9) is considered to be a regulator of IRI, which induces liver apoptosis by reducing the expression of SIRT1 and the level of acetyl-p53 [ 96 ].…”

A two-circular RNA signature of donor circFOXN2 and circNECTIN3 predicts early allograft dysfunction after liver transplantation

“…Xie et al also demonstrated that miR-135b-5p inhibition could protect cardiomyocytes from IRI in a mouse model through the JAK2/STAT3 pathway (26). Furthermore, Xing et al found that miR-27a-5p was upregulated during hepatic IRI in mice (27). In addition, a previous study found that miR-133a-5p reversed the protective effect of propofol in a rat hepatic IRI model (28).…”

Potentially Functional microRNA-mRNA Regulatory Networks in Intestinal Ischemia-Reperfusion Injury: A Bioinformatics Analysis

“… 26 MiR-27a-5p had been associated with a decreased level of Bach1 mRNA, which reduced apoptosis in liver ischemia-reperfusion injury. 27 Elsewhere, miR-1247-3p alleviated the damage of myocardial ischemia-reperfusion by targeting both BCL2L11 and caspase-2. 28 In addition, miR-1247-3p reduced apoptosis of cerebral neurons and could exert protective effects against brain stroke.…”