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Background Pneumonia is becoming increasingly prevalent, and its severity has been continuously escalating, bringing significant damage and stress to people’s lives. The regulatory role of RP11-773H22.4 in the onset and development of severe pneumonia is emerging as an important factor, however, the exact mechanisms controlling its effects have not been fully elucidated. Methods ROC and Kaplan-Meier curves were used to assess the diagnostic and prognostic significance of RP11-773H22.4 in severe pneumonia. qRT-PCR was used to assess the RP11-773H22.4 and miR-1287-5p expression. The CCK-8 was used to assess cell viability. The rate of apoptosis was measured using flow cytometry. The concentration of inflammatory factors was detected using an ELISA kit. The interaction between RP11-773H22.4 and miR-1287-5p was verified by dual luciferase reporter gene assay. Results In individuals afflicted with severe pneumonia, there was an observed up-regulation in RP11-773H22.4 expression and a corresponding decline in miR-1287-5p expression. RP11-773H22.4 demonstrated diagnostic and prognostic significance for severe pneumonia. RP11-773H22.4 augmented the viability of MRC-5 cells with LPS treatment by modulating miR-1287-5p, leading to a reduction in apoptosis and lower levels of inflammatory cytokines. Conclusion RP11-773H22.4 was highly expressed in severe pneumonia and may serve as a diagnostic and prognostic marker for severe pneumonia. miR-1287-5p was downregulated in severe pneumonia, and RP11-773H22.4 participated in the pathogenesis of severe pneumonia by regulating the expression of miR-1287-5p.