Wang Shiqi, He Fuwei, Li Zhenwei, Hu Yewen, Huangfu Ning, Xie Daqi
Department of Cardiology, Ningbo First Hospital No. 59, Liuding Street, Ningbo 315000, PR China.
Department of Cardiology, Ningbo Ninth Hospital No. 68, Xiajia Road, Ningbo 315000, PR China.
Int J Clin Exp Pathol. 2020 Nov 1;13(11):2840-2852. eCollection 2020.
Myocardium functions as an immune organ, and myocardial ischemia-reperfusion (I/R) is known to initiate myocardial innate immune response to induce myocardial injury. However, the mechanisms underlying interferon-β (IFN-β)-mediated myocardial injury during I/R and whether long non-coding RNAs (lncRNAs) are involved in IFN-β-mediated myocardial injury remain unknown. This study identified that I/R significantly induced IFN-β expression in induced pluripotent stem cell-derived cardiomyocytes, and IFN-β further enhanced I/R-induced myocardial apoptosis. Furthermore, it was demonstrated that the lncRNA BRAF-activated non-coding RNA (BANCR) was highly expressed in cardiomyocytes, and BANCR-knockdown suppressed signal transducer and activator of transcription 1 (STAT1) phosphorylation and IFN-β-induced cardiomyocyte apoptosis. Furthermore, it was identified that BANCR specifically interacted with STAT1 to promote IFN-β-STAT1 signaling and enhanced the expression of pro-apoptotic interferon stimulated genes. Overall, the present study reports that lncRNA BANCR promotes IFN-β-mediated cardiomyocyte apoptosis following I/R injury by interacting with STAT1, suggesting lncRNA BANCR is involved in IFN-β-induced cardiomyocyte apoptosis.
心肌作为一个免疫器官发挥作用，已知心肌缺血再灌注（I/R）会引发心肌固有免疫反应以诱导心肌损伤。然而，I/R期间干扰素-β（IFN-β）介导心肌损伤的机制以及长链非编码RNA（lncRNAs）是否参与IFN-β介导的心肌损伤仍不清楚。本研究发现，I/R显著诱导诱导多能干细胞衍生的心肌细胞中IFN-β表达，并且IFN-β进一步增强I/R诱导的心肌细胞凋亡。此外，研究表明长链非编码RNA BRAF激活非编码RNA（BANCR）在心肌细胞中高表达，敲低BANCR可抑制信号转导和转录激活因子1（STAT1）磷酸化以及IFN-β诱导的心肌细胞凋亡。此外，研究发现BANCR与STAT1特异性相互作用，促进IFN-β-STAT1信号传导并增强促凋亡干扰素刺激基因的表达。总体而言，本研究报告lncRNA BANCR通过与STAT1相互作用促进I/R损伤后IFN-β介导的心肌细胞凋亡，提示lncRNA BANCR参与IFN-β诱导的心肌细胞凋亡。
