LncRNA MIR503HG serves as a diagnostic biomarker in patients with sepsis and regulates sepsis-induced inflammation...

Sepsis often has a dysregulated inflammatory response and is accompanied by cardiac dysfunction. This study aimed to explore the mechanism of long non-coding RNA MIR503HG (MIR503HG) in regulating sepsis and the inflammatory responses, and sepsis-induced cardiac dysfunction (SICD). 102 sepsis patients were divided into an SICD group (n = 31) and a non-SICD group (n = 71). A cecal ligation and puncture (CLP) sepsis rat model was constructed. Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to evaluate the target gene expression. Enzyme-linked immunosorbent assay was used to measure the levels of myocardial damage markers and inflammatory factors. RNA immunoprecipitation and Dual luciferase assay were used to determine the targeting relationship. Kyoto Encyclopedia of Genes and Genomes analysis was used to predict signaling pathways of target genes. MIR503HG expression was significantly down-regulated in sepsis patients and SICD patients, and it has good diagnostic value for these two types of diseases. Its expression was significantly negatively correlated with myocardial injury markers (cardiac troponin I [cTnI], creatine kinase-MB [CK-MB]), cardiac function indicators (left ventricular ejection fraction), inflammatory factors (interleukin-6, tumor necrosis factor-alpha), and disease severity scores (Sequential Organ Failure Assessment, Acute Physiology and Chronic Health Evaluation II). Furthermore, it exerted a protective effect in sepsis: MIR503HG overexpression could effectively alleviate SICD and mitigate the inflammatory response, as evidenced by decreased left ventricular end-diastolic pressure, increased left ventricular systolic pressure, reduced levels of CK-MB and cTnI, as well as restored myocardial systolic/diastolic capacity (maximal rate of left ventricular pressure rise/fall [±dP/dt]). Mechanistically, MIR503HG functions as a molecular sponge that sequesters microRNA-497-5p (miR-497-5p), thereby lifting brain-derived neurotrophic factor (BDNF). Delivery of miR-497-5p-agomiR partially offset the cardioprotective and anti-inflammatory effects of MIR503HG, whereas overexpression of BDNF partially restored them. MIR503HG relieved sepsis and reduced cardiac dysfunction and inflammatory response by regulating the miR-497-5p/BDNF axis.