LncRNA HCP5 acts as a potential diagnostic biomarker and attenuates the inflammatory response in neonatal sepsis by targeting miR-138-5p/SIRT1

Introduction:
This study aimed to investigate the clinical significance and potential mechanism of long non-coding RNA human histocompatibility leukocyte antigen complex P5 (HCP5) in neonatal sepsis (NS).

Material and methods:
The study enrolled 86 patients with NS and 80 neonates with respiratory tract infection or pneumonia. The Pearson correlation coefficient was used to evaluate the association of procalcitonin (PCT), C-reactive protein (CRP), and inflammatory factors with HCP5. Serum levels of HCP5 were measured using RT-qPCR. The diagnostic potential of HCP5 was assessed via a receiver operating characteristic (ROC) curve. An in vitro model was established using lipopolysaccharide (LPS)-induced RAW264.7 macrophages. ELISA was conducted to measure the levels of inflammatory factors. Finally, the target relationship was validated using a dual-luciferase reporter assay.

Results:
HCP5 was significantly lower in patients with NS and it negatively correlated with PCT, CRP, interleukin (IL)-8, and tumor necrosis factor α (TNF-α). The area under the ROC curve was 0.902, and the sensitivity and specificity for identifying NS from controls were 86.30% and 83.72%, respectively. In LPS-induced RAW264.7, the levels of HCP5 decreased in a time- and dose-dependent manner. miR-138-5p, a target miRNA for HCP5, was found to be elevated in NS patients. Furthermore, HCP5 significantly reduced LPS-induced overproduction of inflammatory factors, but miR-138-5p reversed this reduction. Furthermore, sirtuin 1 (SIRT1) is a downstream target of miR-138-5p.

Conclusions:
HCP5 could potentially serve as a diagnostic biomarker for NS and it may inhibit inflammation in NS by targeting miR-138-5p/SIRT1 axis. These findings highlight the potential role of HCP5 in the diagnosis and treatment of NS.