Accumulating studies have recognized microRNAs (miRs) and long noncoding RNAs (lncRNAs) as important molecules involved in the mediation of various biological processes, including innate immunity. In this study, we investigated a novel noncoding RNA regulatory circuitry in the immunity during sepsis. A cecal ligation and puncture-induced sepsis mouse model was established to determine the expression of mast cell expression membrane protein 1 (MCEMP1). The RNA crosstalk among lncRNA nuclear enriched abundant transcript 1 (NEAT1), miR-125, and MCEMP1 was validated. Subsequently, the levels of lncRNA NEAT1, miR-125, and MCEMP1 in T lymphocytes isolated from sepsis mice were up- or downregulated by exogenous transfection in an attempt to investigate their effects on the release of inflammatory factors, the expression of immunoglobulins, the activity of T cell subsets and natural killer (NK) cells, as well as T lymphocyte apoptosis. In sepsis mice, MCEMP1 was highly expressed and verified to be a target gene of miR-125. RNA crosstalk experiment revealed that lncRNA NEAT1 directly inhibited miR-125 to upregulate MCEMP1. We also observed that elevation of miR-125, depletion of MCEMP1, or downregulation of lncRNA NEAT1 resulted in promoted T lymphocyte activity, immunoglobulin expression, and NK cell activity, and inhibited release of inflammatory factors and T lymphocyte apoptosis. Taken together, these findings provided evidence that the downregulation of lncRNA NEAT1 could promote miR-125 to exert an inhibitory effect on the immunity in septic mice by suppressing MCEMP1, highlighting a potential target for the treatment of sepsis. © 2019 IUBMB Life, 2019.
Keywords: immunity; long noncoding RNA NEAT1; mast cell expressed membrane protein 1; microRNA-125; sepsis.
© 2019 International Union of Biochemistry and Molecular Biology.