Key m(6)A regulators mediated methylation modification pattern and immune infiltration characterization in hepatic ischemia-reperfusion injury

BACKGROUND: N(6)-methyladenosine (m(6)A) mRNA modification plays a critical role in various human biological processes. However, there has been no study reported to elucidate its role in hepatic ischemia-reperfusion injury (IRI). This study was aimed to explore the expression pattern together with the potential functions of m(6)A regulators in hepatic IRI. METHODS: The gene expression data (GSE23649) of m(6)A regulators in human liver tissue samples before cold perfusion and within 2 h after portal vein perfusion from Gene Expression Omnibus database was analyzed. The candidate m(6)A regulators were screened using random forest (RF) model to predict the risk of hepatic IRI. The evaluation of infiltrating abundance of 23 immune cells was performed using single sample gene set enrichment analysis. Besides, quantitative real time polymerase chain reaction (qRT-PCR) assay was carried out to validate the expression of key m(6)A regulators in mouse hepatic IRI model. RESULTS: The expressions of WTAP, CBLL1, RBM15, and YTHDC1 were found to be increased in liver tissues 2 h after portal vein perfusion; in contrast, the expressions of LRPPRC, FTO, METTL3, and ALKBH5 were decreased. Based on RF model, we identified eight m(6)A methylation regulators for the prediction of the risk of hepatic IRI. Besides, a nomogram was built to predict the probability of hepatic IRI. In addition, the levels of WTAP, ALKBH5, CBLL1, FTO, RBM15B, LRPPRC and YTHDC1 were correlated with the immune infiltration of activated CD4 T cell, activated dendritic cell (DC), immature DC, mast cell, neutrophil, plasmacytoid DC, T helper (Th) cell (type 1, 2, and 17), gamma delta T cell, T follicular helper (Tfh) cell, myeloid-derived suppressor cell (MDSC), macrophage, natural killer cell, and regulatory Th cell. Among mouse hepatic IRI model, the mRNA level of CBLL1 and YTHDC1 was increased with statistical significance; however, the mRNA level of FTO and METTL3 was decreased among post-reperfusion liver samples compared with those in pre-reperfusion samples with statistical significance. CONCLUSIONS: The m(6)A regulators exerted a pivotal impact on hepatic IRI. The m(6)A patterns that found in this study might provide novel targets and strategies for the alleviation/treatment of hepatic IRI in the future. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12920-023-01751-0.