Silencing of long non-coding RNA MALAT1 suppresses inflammation in septic mice: role of microRNA-23a in the down-regulation of MCEMP1 expression.

Abstract

Sepsis is a life-threatening disease without ideal biomarkers. Some long non-coding RNAs (lncRNAs) are found to be implicated in sepsis. Thus, we investigated the effects of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on inflammation in septic mice and the potential mechanisms of the MALAT1/microRNA-23a (miR-23a)/MCEMP1 axis. The sepsis mice model was generated by cecal ligation and puncture (CLP). Then the expressions of lncRNA MALAT1, mast cell-expressed membrane protein 1 (MCEMP1), and miR-23a in septic mice were determined. The interaction between lncRNA MALAT1, miR-23a and MCEMP1 was confirmed. Loss- and gain-of-function approaches were used to verify the roles of the lncRNA MALAT1, miR-23a, and MCEMP1 in inflammation, cell proliferation and apoptosis in septic mice. The myeloperoxidase (MPO) activity and the expression of interleukin 6 (IL-6), IL-1β, IL-10, and tumor necrosis factor-α (TNF-α) were detected. High expression of the lncRNA MALAT1 and MCEMP1, as well as low expression of miR-23a, was observed in septic mice. LncRNA MALAT1 competitively bound to miR-23a, and miR-23a targeted MCEMP1. Moreover, the down-regulation of lncRNA MALAT1 repressed the expression of MPO, IL-6, IL-10, TNF-α, and IL-1β. Silencing of lncRNA MALAT1 or overexpression of miR-23a reduced inflammation, inhibited cell proliferation, and promoted cell apoptosis in septic mice. Taken together, MALAT1 promotes the inflammation in septic mice by binding to miR-23a to up-regulate MCEMP1. Therefore, silencing of lncRNA MALAT1 might provide a novel therapeutic target for sepsis.