Downregulation of circular RNA_102928 contributes to lung inflammation and epithelial apoptosis in smoke inhalation injury

Smoke inhalation injury is the leading cause of mortality in patients with burns. Circular RNAs (circRNAs) are a class of endogenous noncoding RNAs implicated in various diseases. However, their specific involvement in smoke inhalation injury remains poorly understood. High-throughput microarray analysis was used to identify differentially expressed circRNAs in plasma samples from patients with smoke inhalation injury compared to healthy controls. Five circRNAs were initially identified, and three were validated by quantitative real-time PCR (qRT-PCR). Bioinformatic analysis was used to establish circRNA–miRNA–mRNA networks. The predicted circRNA-miRNA-mRNA axes were further investigated in a rat inhalation injury model and in A549 cells. Microarray analysis revealed 65 differentially expressed circRNAs, of which three (hsa_circRNA_102928, hsa_circRNA_102059, and hsa_circRNA_101115) were confirmed by qRT-PCR, with one downregulated and two upregulated circRNAs. Bioinformatic analysis predicted 11 potential circRNA-microRNA-mRNA axes associated with smoke inhalation injury development, including the circRNA_102928/let-7f-2-3p/MDM1 axis. In a smoke inhalation injury rat model, the downregulation of circRNA_102928 and MDM1 mRNA, as well as the upregulation of let-7f-2-3p expression, coincided with prominent inflammation in the lungs. Overexpression of circRNA_102928 dramatically reduced let-7f-2-3p and significantly increased MDM1 mRNA levels in A549 cells. Furthermore, circRNA_102928 overexpression notably mitigated tumor necrosis factor-alpha and interleukin 1 beta expression and attenuated apoptosis in A549 cells. This study highlighted the role of the circRNA_102928/let-7f-2-3p/MDM1 axis in mediating lung inflammation and epithelial apoptosis in wood smoke inhalation injuries. Plasma samples were collected from five patients with smoke inhalation injuries on the third day who were admitted to the hospital within 24 hours after injury. Five plasma samples were collected from sex- and age-matched healthy volunteers as controls.