CircRNA-Phf21a_0002 promotes pyroptosis to aggravate hepatic ischemia/ reperfusion injury by sponging let-7b-5p
Peng Jiang,
Xinqiang Li,
Yuntai Shen,
Lijian Luo,
Bin Wu,
Dahong Teng,
Jinshan Wang,
Imran Muhammad,
Qingguo Xu,
Shipeng Li,
Bin Zhang,
Jinzhen Cai
Affiliations
Peng Jiang
The Institute of Transplantation Science, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China; Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
Xinqiang Li
The Institute of Transplantation Science, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China; Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
Yuntai Shen
The Institute of Transplantation Science, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China; Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
Lijian Luo
Organ Transplant Center, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
Bin Wu
Organ Transplant Center, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
Dahong Teng
Organ Transplant Center, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
Jinshan Wang
Organ Transplant Center, Fujian Medical University Union Hospital, Fuzhou, Fujian, China
Imran Muhammad
The Institute of Transplantation Science, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China; Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
Qingguo Xu
Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China
Shipeng Li
Department of Hepatopancreaticobiliary Surgery, Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, China; Corresponding author.
Bin Zhang
Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China; Corresponding author.
Jinzhen Cai
Organ Transplant Center, Fujian Medical University Union Hospital, Fuzhou, Fujian, China; The Institute of Transplantation Science, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China; Organ Transplantation Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China; Corresponding author. Organ Transplant Center, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
Hepatic ischemia‒reperfusion injury is a common injury in liver surgery and liver transplantation that can lead to liver function damage, including oxidative stress, apoptosis, autophagy and inflammatory reactions. Pyroptosis is a type of inflammatory programmed cell death that has been implicated in ischemia‒reperfusion injury-associated inflammatory reactions. Although circular RNAs can regulate cell death in hepatic ischemia‒reperfusion injury, their relationship with pyroptosis remains unclear. Therefore, this study aimed to investigate the effect of circular RNA on pyroptosis in hepatic ischemia‒reperfusion injury. We constructed a mouse hepatic ischemia‒reperfusion injury model for circular RNA sequencing and obtained 40 circular RNAs with significant differential expression, of which 39 were upregulated and 1 was downregulated. Subsequently, the endogenous competitive RNA network was constructed using TarBase, miRTarBase, TargetScan, RNAhybrid, and miRanda. Gene Set Enrichment Analysis, Kyoto Encyclopedia of Genes and Genomes and Gene Ontology functional analyses of downstream target genes revealed that circRNA-Phf21a_0002 might affect pyroptosis by regulating the mTOR signaling pathway and Bach1 by sponging let-7b-5p. The overexpression plasmid upregulated the expression of circRNA-Phf21a_0002 in a hypoxia/reoxygenation model, which aggravated pyroptosis in AML12 cells and apoptosis and necrosis of hepatocytes. Next, we investigated the underlying mechanism and found that circRNA-Phf21a_0002 enabled the expression of Bach1 through sponging of let-7b-5p. The aggravation of pyroptosis via overexpression of circRNA-Phf21a_0002 was reversed by let-7b-5p mimics in hypoxia/reoxygenation-subjected AML12 cells. Collectively, our study clarifies that circRNA-Phf21a_0002 aggravates the pyroptosis of hepatocytes related to ischemia-reperfusion by sponging let-7b-5p. These findings provide new molecular mechanisms and novel biomarkers for follow-up treatment.
