Dysregulated expression of the EMX2OS/miR-34c-5p/TBL1XR1 regulatory axis: a novel signature for severe community-acquired pneumonia in children

Abstract

Molecular pathology of severe community acquired pneumonia (SCAP) stays undefined; EMX2OS displays dysregulated expression in inflammation-related conditions, meriting exploration of its SCAP role. This study sought to investigate the expression pattern and clinical significance of EMX2OS in SCAP. Serum samples were collected from SCAP patients and healthy controls. RT-qPCR was employed to measure expression levels of EMX2OS, miR-34c-5p, and TBL1XR1 in serum and in LPS-stimulated BEAS-2B cells. Cell viability was assessed using CCK-8 assay, apoptosis was evaluated by flow cytometry, and inflammatory cytokines TNF-α, IL-1β, and IL-6 were quantified by ELISA. Oxidative stress and ferroptosis markers including MDA, GSH, and iron were determined using commercial kits. Molecular interactions were verified by dual-luciferase reporter assay and RNA immunoprecipitation. Serum EMX2OS and TBL1XR1 were upregulated whereas miR-34c-5p was downregulated in SCAP patients; EMX2OS demonstrated diagnostic utility and served as a risk factor. In LPS-stimulated BEAS-2B cells, EMX2OS and TBL1XR1 increased while miR-34c-5p decreased, accompanied by reduced viability, enhanced apoptosis, elevated inflammatory cytokines, and aberrant oxidative stress and ferroptosis markers, all of which were reversed by EMX2OS silencing. EMX2OS bound directly to and negatively regulated miR-34c-5p, which in turn bound directly to and suppressed TBL1XR1. Rescue experiments revealed that miR-34c-5p inhibition partially restored cellular injury phenotypes under EMX2OS silencing, and additional TBL1XR1 knockdown reversed these effects. Our findings suggest that EMX2OS is associated with inflammation, oxidative stress, and ferroptosis in SCAP, potentially by sponging miR-34c-5p to upregulate TBL1XR1.