Tripartite Motif-containing 32 Regulated by MiR-6236-p5 Inhibited Silica-induced Apoptosis of Alveolar Macrophages

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.