LncRNA SNHG1 promotes sepsis-induced myocardial injury by inhibiting Bcl-2 expression via DNMT1

Abstract

Myocardial injury is a frequently occurring complication of sepsis. This study aims to investigate the molecular mechanism of long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1)-mediated DNA methyltransferase 1/B-cell lymphoma-2 (DNMT1/Bcl-2) axis in sepsis-induced myocardial injury. Mice and HL-1 cells were treated with lipopolysaccharide (LPS) to establish animal and cellular models simulating sepsis and inflammation. LncRNA SNHG1 was screened out as a differentially expressed lncRNA in sepsis samples through microarray profiling, and the upregulated expression of lncRNA SNHG1 was confirmed in myocardial tissues of LPS-induced septic mice and HL-1 cells. Further experiments suggested that silencing of lncRNA SNHG1 reduced the inflammation and apoptotic rate of LPS-induced HL-1 cells. LncRNA SNHG1 inhibited Bcl-2 expression by recruiting DNMT1 to Bcl-2 promoter region to cause methylation. Inhibition of Bcl-2 promoter methylation reduced the inflammation and apoptotic rate of LPS-induced HL-1 cells. In vivo experiments substantiated that lncRNA SNHG1 silencing alleviated sepsis-induced myocardial injury in mice. Taken together, lncRNA SNHG1 promotes LPS-induced myocardial injury in septic mice by downregulating Bcl-2 through DNMT1-mediated Bcl-2 methylation.

Keywords: B-cell lymphoma-2; DNA methyltransferase 1; inflammation; long noncoding RNA; methylation; myocardial injury; sepsis; small nucleolar RNA host gene 1.