LncRNA MIR155HG Accelerates the Progression of Sepsis via Upregulating MEF2A by Sponging miR-194-5p.

Abstract

Long noncoding RNA MIR155HG exerts important effects in the progression of multiple diseases. This study investigated the functions of MIR155HG in sepsis development. Blood samples were collected from 28 patients with sepsis and 28 without sepsis. The murine cardiac muscle cell line (HL-1) and macrophage cell line (RAW 264.7) treated with lipopolysaccharide (LPS) were used as the in vitro sepsis models. The levels of MIR155HG, miR-194-5p, and MEF2A were determined using real-time-quantitative polymerase chain reaction. Cell counting kit-8 and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays were used to assess cell viability and apoptosis, respectively. The association between miR-194-5p and MIR155HG or MEF2A was confirmed using a dual-luciferase reporter assay. The levels of inflammatory cytokines were detected using enzyme-linked immunosorbent assay (ELISA). In this study, we demonstrated that MIR155HG expression was significantly increased in sepsis blood samples, RAW 264.7, and HL-1 cells treated with LPS. Silencing of MIR155HG promoted cell viability and obstructed cell apoptosis and inflammation of RAW 264.7 and HL-1 cells treated with LPS. MiR-194-5p depletion abrogated cell viability promotion and suppressive effect on cell apoptosis and inflammation caused by MIR155HG knockdown. In addition, MIR155HG upregulated MEF2A through interaction with miR-194-5p. Finally, rescue assays indicated that MEF2A overexpression abolished the inhibitory effect on sepsis progression induced by MIR155HG deletion. In conclusion, MIR155HG promotes sepsis progression in an in vitro sepsis model by modulating the miR-194-5p/MEF2A axis. This discovery provides a promising biomarker for sepsis therapy.