Tripartite motif-containing 32 regulated by miR-6236-p5 inhibited silica-induced apoptosis of alveolar macrophages.

Abstract

Apoptosis of alveolar macrophages (AMs) induced by silica is one of the crucial driving factors of silicosis inflammation and fibrosis. However, the mechanism of silica-induced AMs apoptosis remains unclear. In this study, transcriptome sequencing identified 11 differentially expressed (DE)-mRNAs enriched in the regulation of apoptotic signaling pathways in AMs treated with 250 μg/mL silica for 24 h, of which tripartite motif-containing 32 (Trim32) was the most significant and down-regulated. The decreased Trim32 promoted AMs apoptosis, while Trim32 overexpression inhibited the apoptosis of AMs induced by silica at 250 μg/mL for 24 h. MiR-6236-p5 was then identified by MiRNA sequencing as the most significant DE-miRNA potentially regulating Trim32 expression, and the interaction between miR-6236-p5 and Trim32 3'-UTR was confirmed by dual luciferase reporter gene assay. Treated with 100 nM miR-6236-p5 inhibitor increased the expression of Trim32 and inhibited the apoptosis of AMs induced by silica at 250 μg/mL for 24 h, while miR-6236-p5 mimic promoted the apoptosis of silica-induced AMs. In conclusion, this study identified Trim32 regulated by miR-6236-p5 played an important role in silica-induced AMs apoptosis based on RNA sequencing, which provided a novel clue for exploring the mechanism of silica-induced AMs apoptosis.