Clinical Significance of miR-766-3p in Severe Pneumonia in Children and Its Associated Molecular Mechanisms.

Abstract

Introduction: Severe pneumonia in children is a critical cause of childhood mortality. miR-766-3p is a known anti-inflammatory factor. The aim of our study is to investigate the clinical value of miR-766-3p and the molecular mechanisms by which miR-766-3p regulates severe pneumonia.

Methods: The relative levels of miR-766-3p in participants' plasma were detected by quantitative real-time PCR (RT-qPCR). The diagnostic performance and prognostic value of miR-766-3p were assessed using receiver operating characteristic (ROC) curves, Kaplan-Meier curves, and Cox regression models. In vitro, lipopolysaccharide (LPS) was employed to mimic the pneumonia environment. Cell viability was tested by Cell Counting Kit-8 (CCK-8) assay. The levels of inflammatory factor were measured via RT-qPCR and enzyme-linked immunosorbent assay (ELISA).

Results: The levels of miR-766-3p were decreased by 0.36-fold in children with severe pneumonia, and it effectively distinguished between children with severe pneumonia and healthy children. In pediatric patients, the accumulative survival rate was lower in low miR-766-3p expression group (average miR-766-3p level ≤ 0.65) compared to high expression group (average miR-766-3p level > 0.65). Multivariable Cox proportional-hazards regression model analysis indicated that miR-766-3p was an independent risk factor for poor patient outcomes. Moreover, miR-766-3p mimic attenuated the inhibition of cell viability and interleukin-10 (IL-10) levels as well as the promotion of levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) caused by LPS. These effects were further abolished by Mucin 19 (MUC19) upregulation.

Conclusion: miR-766-3p has potential as a diagnostic and prognostic biomarker. Mechanistically, miR-766-3p alleviates LPS-induced inflammation in MRC-5 cells by modulating MUC19.