LncRNA RP11-284N8.3 regulates the expression and alternative splicing of genes associated with sepsis-induced acute lung injury
Sepsis-induced acute lung injury (ALI) poses a significant threat to human health,  necessitating further investigation into its underlying mechanisms. Long noncoding RNAs (lncRNAs) have emerged as key regulators in various diseases, including sepsis. In our prior research, we observed significant downregulation of lncRNA RP11-284N8.3 in the blood samples of sepsis patients. Herein, we elucidate the functional role and regulatory molecular targets of RP11-284N8.3 in lipopolysaccharide (LPS)-exposed BEAS-2B cells. Initially, we found that LPS treatment notably repressed RP11-284N8.3 expression. However, overexpression of RP11-284N8.3 significantly promoted cell proliferation, inhibited apoptosis, and attenuated IL-1ß expression in response to LPS stimulation, indicative of its anti-inflammatory properties. Further RNA-seq analysis revealed that RP11-284N8.3 might have contributed to the significant down-regulation of genes associated with the inflammatory response, while genes related to cell cycle/division and apoptosis underwent alternative splicing (AS) deregulation. Finally, RT-qPCR was used to validate differentially expressed genes (DEGs) (ICAM5, GDF15, NECTIN4,  SERPINB2) and AS genes (IL24, APEX1, PVT1, HNRNPUL1) regulated by RP11-284N8.3,  consistent with transcriptome changes. In summary, RP11-284N8.3 has a significant global regulatory effect in LPS-treated BEAS-2B cells and its possible protective role against sepsis-induced ALI. We propose RP11-284N8.3 and its downstream targets as potential therapeutic targets for sepsis management in the future. Overall design: RNA-seq of RP11-284N8.3 overexpression versus control in BEAS-2B cells aims to comprehensively characterize the functional role of lncRNA RP11-284N8.3 in lipopolysaccharide (LPS)-induced ALI through transcriptomic (RNA-seq) analyses, including differentially expressed gene (DEG) and alternative splicing (AS) profiling.