LncRNA CAIF suppresses LPS-induced inflammation and apoptosis of cardiomyocytes through regulating miR-16 demethylation.

backgroundThe long noncoding RNA, cardiac autophagy inhibitory factor (CAIF), and microRNA (miR)-16 are reported to be involved in lipopolysaccharide (LPS)-induced inflammatory responses and cell apoptosis in many diseases. Herein, we investigated the interaction between CAIF and miR-16 in sepsis-induced chronic heart failure (CHF).

methodsThe expression of CAIF and miR-16 in plasma samples from sepsis-induced CHF patients (n = 60) and healthy controls (n = 60) were measured using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The correlations between CAIF and miR-16 across plasma samples from patients with sepsis-induced CHF and healthy controls were analyzed using linear regression. The messenger RNA (mRNA) levels of inducible nitric oxide synthase, C-C motif chemokine 2 (CCL2), growth-regulated alpha protein (CXCL1), and interleukin-6 (IL-6) were evaluated using qRT-PCR while nuclear factor κB activation was evaluated using luciferase assay.

resultsThe expression levels of CAIF and miR-16 were downregulated in the plasma of sepsis-induced CHF patients and were positively correlated in these patients. In cardiomyocytes, LPS treatment dose-dependently decreased CAIF and miR-16 levels. CAIF overexpression increased miR-16 expression by demethylating miR-16. CAIF and/or miR-16 overexpression suppressed LPS-induced CCL2, CXCL1, and IL-6 expression at both the mRNA and protein levels. Analysis of cell apoptosis and western blot analysis showed that CAIF and/or miR-16 overexpression inhibited LPS-induced cardiomyocyte apoptosis by reducing Bax and cleaved caspase 3 levels and enhancing Bcl-2 levels.

conclusionOur study is the first to report the abnormal expression of CAIF and miR-16 in heart disease. CAIF plays a protective role in sepsis-induced CHF by inhibiting cardiomyocyte apoptosis and inflammation, possibly by regulating miR-16 demethylation.