Long non-coding RNA small nucleolar RNA host gene 8 (SNHG8) sponges miR-34b-5p to prevent sepsis-induced cardiac dysfunction and inflammation and serves as a diagnostic biomarker.

Abstract

Introduction: The study aimed to evaluate, for the first time, the diagnostic value of long non-coding RNA (lncRNA) small nucleolar RNA host gene 8 (SNHG8) in sepsis and its molecular mechanisms in sepsis-induced inflammation and cardiac dysfunction.

Material and methods: A total of 126 sepsis patients and 81 healthy controls were enrolled. Serum SNHG8 levels were assessed by RT-qPCR. Levels of pro-inflammatory factors were examined via ELISA. The ROC curve was employed to assess the diagnostic significance of SNHG8. Cardiomyocytes were exposed to lipopolysaccharide (LPS) to simulate sepsis-induced cardiac dysfunction in vitro. Cell proliferation and apoptosis were measured through CCK-8 and flow cytometry. Dual luciferase reporter gene assay and RIP assay were conducted to verify the target relationship between SNHG8 and miR-34b-5p.

Results: SNHG8 was reduced in sepsis patients (p < 0.05) and negatively correlated with procalcitonin, C-reactive protein, and pro-inflammatory factors (p < 0.05). SNHG8 had outstanding performance in distinguishing sepsis patients from healthy individuals with the AUC of 0.878. Among septic patients, those with cardiac dysfunction had significantly downregulated SNHG8 levels (p < 0.05). For septic patients, SNHG8 was found to be an independent predictor for the occurrence of cardiac dysfunction (HR = 5.466, 95% CI = 2.230-13.397, p < 0.001). Elevated SNHG8 reversed LPS-induced cell apoptosis, and attenuated the over-secretion of inflammatory factors. miR-34b-5p was significantly upregulated in septic patients and negatively correlated with SNHG8, indicating that it acted as a sponge for SNHG8.

Conclusions: Reduced SNHG8 is a potential diagnostic biomarker for sepsis. It is involved in sepsis-induced inflammatory response and cardiac dysfunction through sponging miR-34b-5p.