Author + information
- Yang-Yang Deng1,2,
- Weiping Zhang1,2,
- Jianqing She1,2,
- Lisa Zhang2,
- Tao Chen1,2,
- Juan Zhou1,2 and
- Zuyi Yuan1,2
Circular RNAs (circRNAs) has been implicated in the development of various diseases, but there is little knowledge of circRNAs in acute myocardial infarction (AMI). Previous study have demonstrated that PPARγ can protect heart from AMI. The aim of this study was to identify circRNA expression in human AMI and to explore the function of PPARγ-related circRNAs in AMI.
To identify circRNAs that are specifically expressed in AMI, we compared plasma expression of circRNAs in AMI patients with healthy volunteers (AMI group vs. Con group, Arraystar CircRNA Microarray). PPARγ expression and activity were also detected by western blot. Bioinformatics analysis was employed to predict the interaction of circRNAs and PPARγ mRNAs in AMI. Loss-of-function and rescue experiments were then performed in vitro.
7326 circRNAs were detected in the plasma samples, of which 160 were differentially expressed between AMI group and Con group (73 up-regulated and 87 down-regulated, >2 folds, p<0.05). Especially, circRNA_081881 was significantly down-regulated in AMI group (12.5 fold, p<0.05). What's more, PPARγ expression (156±12%, p<0.05) and activity were significantly lower in AMI group than in Con group. Bioinformatics analysis (mirWalk database) show that hsa-miR-548 is related to PPARG gene (p<0.01). Meanwhile, miRNA GO analysis show that 7 different binding sites of miR-548 can be found in circRNA_081881 sequence. Loss-of-function and rescue experiments show that circRNA_081881 expression increased with interleukin-1 (IL-1) and tumor necrosis factor (TNF-α) levels in macrophages (n=6, p<0.05). Silencing of circRNA_081881 using small interfering RNA suppressed PPARγ expression, decreased M2 polarization and increased foam cell formation (n=6, p<0.05). CircRNA_081881 could compete for miR-548 with PPARγ.
Our results demonstrated that circRNA_081881 regulated PPARγ expression by functioning as a competing endogenous RNA (ceRNA) of miR-548. These data suggest that circRNA_081881 in plasma may be used as a potential target for the precision diagnosis and therapy of AMI.