IFN regulatory Factor-1 induced macrophage pyroptosis by modulating m6A modification of circ_0029589 in patients with acute coronary syndrome |
| |
| Affiliation: | 1. Department of Cardiology, First Hospital of Shanxi Medical University, Taiyuan, China;2. Shanxi Medical University, Taiyuan, China;3. Department of Cardiology, the People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, China |
| |
| Abstract: | BackgroundPyroptosis is identified as a novel form of inflammatory programmed cell death and has been recently found to be closely related to atherosclerosis (AS). We found that IFN regulatory factor-1(IRF-1) effectively promotes macrophage pyroptosis in patients with acute coronary syndrome (ACS). Subsequent studies have demonstrated that circRNAs are implicated in AS. However, the underlying mechanisms of circRNAs in macrophage pyroptosis remain elusive.MethodsWe detected the RNA expression of hsa_circ_0002984, hsa_circ_0010283 and hsa_circ_0029589 in human PBMC-derived macrophages from patients with coronary artery disease (CAD). The lentiviral recombinant vector for hsa_circ_0029589 overexpression (pLC5-GFP-circ_0029589) and small interference RNAs targeting hsa_circ_0029589 and METTL3 were constructed. Then, macrophages were transfected with pLC5-GFP-circ_0029589, si-circ_0029589 or si-METTL3 after IRF-1 was overexpressed and to explore the potential mechanism of hsa_circ_0029589 involved in IRF-1 induced macrophage pyroptosis.ResultsThe relative RNA expression level of hsa_circ_0029589 in macrophages was decreased, whereas the N6-methyladenosine (m6A) level of hsa_circ_0029589 and the expression of m6A methyltransferase METTL3 were validated to be significantly elevated in macrophages in patients with ACS. Furthermore, overexpression of IRF-1 suppressed the expression of hsa_circ_0029589, but induced its m6A level along with the expression of METTL3 in macrophages. Additionally, either overexpression of hsa_circ_0029589 or inhibition of METTL3 significantly increased the expression of hsa_circ_0029589 and attenuated macrophage pyroptosis.ConclusionOur observations suggest a novel mechanism by which IRF-1 facilitates macrophage pyroptosis and inflammation in ACS and AS by inhibiting circ_0029589 through promoting its m6A modification. |
| |
| Keywords: | IRF-1 Circ_0029589 N6-methyladenosine Macrophage pyroptosis Atherosclerosis AS" },{" #name" :" keyword" ," $" :{" id" :" k0035" }," $$" :[{" #name" :" text" ," _" :" atherosclerosis IRF-1" },{" #name" :" keyword" ," $" :{" id" :" k0045" }," $$" :[{" #name" :" text" ," _" :" IFN Regulatory Factor-1 ACS" },{" #name" :" keyword" ," $" :{" id" :" k0055" }," $$" :[{" #name" :" text" ," _" :" acute coronary syndrome circRNAs" },{" #name" :" keyword" ," $" :{" id" :" k0065" }," $$" :[{" #name" :" text" ," _" :" circular RNAs CAD" },{" #name" :" keyword" ," $" :{" id" :" k0075" }," $$" :[{" #name" :" text" ," _" :" coronary artery disease DCs" },{" #name" :" keyword" ," $" :{" id" :" k0085" }," $$" :[{" #name" :" text" ," _" :" dendritic cells miRNA" },{" #name" :" keyword" ," $" :{" id" :" k0095" }," $$" :[{" #name" :" text" ," _" :" microRNA VSMCs" },{" #name" :" keyword" ," $" :{" id" :" k0105" }," $$" :[{" #name" :" text" ," _" :" vascular smooth muscle cells m6A" },{" #name" :" keyword" ," $" :{" id" :" k0115" }," $$" :[{" #name" :" text" ," _" :" N6-methyladenosine CPS" },{" #name" :" keyword" ," $" :{" id" :" k0125" }," $$" :[{" #name" :" text" ," _" :" clinical presentation of chest pain SA" },{" #name" :" keyword" ," $" :{" id" :" k0135" }," $$" :[{" #name" :" text" ," _" :" stable angina PBMCs" },{" #name" :" keyword" ," $" :{" id" :" k0145" }," $$" :[{" #name" :" text" ," _" :" Peripheral blood mononuclear cells RNAi" },{" #name" :" keyword" ," $" :{" id" :" k0155" }," $$" :[{" #name" :" text" ," _" :" RNA interference siRNA" },{" #name" :" keyword" ," $" :{" id" :" k0165" }," $$" :[{" #name" :" text" ," _" :" Small interfering RNA EV" },{" #name" :" keyword" ," $" :{" id" :" k0175" }," $$" :[{" #name" :" text" ," _" :" empty vector NC" },{" #name" :" keyword" ," $" :{" id" :" k0185" }," $$" :[{" #name" :" text" ," _" :" nitrocellulose T2DM" },{" #name" :" keyword" ," $" :{" id" :" k0195" }," $$" :[{" #name" :" text" ," _" :" type 2 diabetes mellitus ELISA" },{" #name" :" keyword" ," $" :{" id" :" k0205" }," $$" :[{" #name" :" text" ," _" :" Enzyme-linked immunosorbent assay LDH" },{" #name" :" keyword" ," $" :{" id" :" k0215" }," $$" :[{" #name" :" text" ," _" :" lactate dehydrogenase pNA" },{" #name" :" keyword" ," $" :{" id" :" k0225" }," $$" :[{" #name" :" text" ," _" :" p-nitroanilide NLRP3" },{" #name" :" keyword" ," $" :{" id" :" k0235" }," $$" :[{" #name" :" text" ," _" :" Nucleotide-binding oligomerization domain-like receptor 3 |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
