Lung
ischemia/reperfusion (I/R) injury (LIRI) is a common complication after
lung transplantation,
embolism, and
trauma.
N6-methyladenosine (m6A) methylation modification is implicated in the pathogenesis of I/R injury. However, there are no or few reports of m6A-related regulators in LIRI till now. In this text, dysregulated genes in lung tissues of LIRI rats versus the
sham group were identified by
RNA sequencing (
RNA-seq).
RNA-seq outcomes revealed that only YTH
N6-methyladenosine RNA binding protein 3 (YTHDF3) and
insulin-like growth factor 2
mRNA-
binding protein 2 (IGF2BP2) were differentially expressed in the LIRI versus
sham group among 20 m6A-related regulators. Next, the functions and molecular mechanisms of YTHDF3 and IGF2BP2 in LIRI were investigated in a
hypoxia/reoxygenation-induced BEAS-2B cell injury model in vitro. Results showed that YTHDF3 or IGF2BP2 knockdown attenuated
hypoxia/reoxygenation-mediated inhibitory effects on cell survival and cell cycle progression and inhibited
hypoxia/reoxygenation-induced cell apoptosis and pro-inflammatory
cytokine secretion in BEAS-2B cells. Genes that could be directly regulated by YTHDF3 or IGF2BP2 were identified based on prior experimental data and bioinformatics analysis. Moreover, multiple potential downstream pathways of YTHDF3 and IGF2BP2 were identified by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis of the above-mentioned genes. Among these potential pathways, we demonstrated that YTHDF3 or IGF2BP2 knockdown inhibited
hypoxia/reoxygenation-activated p38, ERK1/2, AKT, and NF-κB pathways in BEAS-2B cells. In conclusion, YTHDF3 or IGF2BP2 knockdown weakened
hypoxia/reoxygenation-induced human lung bronchial epithelial cell injury by inactivating p38, AKT, ERK1/2, and NF-κB pathways.