Comprehensive analysis of circular RNAs from steatotic livers after ischemia and reperfusion injury by next‐generation RNA sequencing

Abstract

Global organ shortage has led to the acceptance of steatotic livers for transplantation, taking the risk of graft dysfunction associated with the higher sensitivity of steatotic livers to ischemia and reperfusion injury (IRI). Data about circular RNAs (circRNAs) in steatotic livers following IRI are practically nonexistent. In our study, a high-fat diet-fed mouse model of hepatic steatosis was generated, and RNA sequencing was performed both on IRI and on sham liver tissues of these mice to screen for circRNAs with significant differential expression. To further validate our bioinformatics data, one upregulated circRNA and four downregulated circRNAs were examined. The circularity of these circRNAs was demonstrated using RNaseR digestion and Sanger sequencing. The expression of four stable circRNAs undigested by RNaseR was further validated by quantitative PCR. In summary, this study unearths several circRNAs as novel and potentially effective targets involved in the more severe damage of steatotic livers following IRI.

Assessing Donor Liver Quality and Restoring Graft Function in the Era of Extended Criteria Donors

“…43 In a cohort of 115 human LTs, Wang et al 44 reported that low levels of donor graft circFOXN2 and circNEXTIN3 that regulated miR-135b-5p and miR-149-5p and had roles in hepatic IRI were associated with the incidence of EAD. In a mice model of IRI (Qu et al 65 identified 13 differentially expressed circRNAs (e.g., Chr3:83031528|83031748, Chr10:89473752|89483524) in postperfusion livers that were involved in more severe IRI in steatotic livers. In a rat LT model, Chen et al 45 demonstrated that lncRNA LOC103692832 in rat grafts was related to early graft injury following LT that was mediated by the expression of apoptosis-related genes like HMOX1 and ATF3.…”

Circular RNA as An Epigenetic Regulator in Chronic Liver Diseases

“…Hepatic ischemia and reperfusion injury (IRI) are major complications during surgical procedures such as liver transplantation, liver resection, and trauma surgery [89]. The comprehensive analysis of circRNAs during hepatic IRI was performed using nextgeneration RNA sequencing [90,91], and several circRNAs were selected as potential targets against hepatic IRI. In the hepatic IRI model established by hepatic artery occlusion, circRNA_017753-miR-218-5p-Jade1, circRNA_017753-miR-7002-3p-Jade1, and circRNA_017753-miR-7008-3p-Jade1 ceRNA signaling pathways may play important roles in the mechanisms of ischemic preconditioning protection [92].…”

hsa_circ_0072389, hsa_circ_0072386, hsa_circ_0008621, hsa_circ_0072387, and hsa_circ_0072391 aggravate glioma via miR-338-5p/IKBIP

“…Circular RNA is a type of noncoding RNA lacking both a 5′ end cap and a 3′ end polytail that induces a circular RNA structure via covalent bonds [ 3 ]. Due to their closed circular structure, circRNAs are seldom degraded by exonuclease, which makes them more stable than linear RNAs [ 4 ]. An increasing number of studies show that circRNAs participate in the occurrence and development of a variety of cancers [ 5 ].…”