Silence of long noncoding RNA NEAT1 exerts suppressive effects on immunity during sepsis by promoting microRNA-125-dependent MCEMP1 downregulation.

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.