Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
J Cell Mol Med. 2022 May;26(10):2895-2907. doi: 10.1111/jcmm.17304. Epub 2022 Apr 3.
Pyroptosis is associated with various cardiovascular diseases. Increasing evidence suggests that long noncoding RNAs (lncRNAs) have been implicated in gene regulation, but how lncRNAs participate in the regulation of pyroptosis in the heart remains largely unknown. In this study, we aimed to explore the antipyroptotic effects of lncRNA FGF9-associated factor (FAF) in acute myocardial infarction (AMI). The expression patterns of lncRNA FAF, miR-185-5p and P21 activated kinase 2 (PAK2) were detected in hypoxia/ischaemia-induced cardiomyocytes. Hoechst 33342/PI staining, lactate dehydrogenase (LDH) release assay, immunofluorescence and Western blotting were conducted to assay cell pyroptosis. The interaction between lncRNA FAF, miR-185-5p and PAK2 was verified by bioinformatics analysis, small RNA sequencing luciferase reporter assay and qRT-PCR. The expression of LncRNA FAF was downregulated in hypoxic cardiomyocytes and myocardial tissues. Overexpression of lncRNA FAF could attenuate cardiomyocyte pyroptosis, improve cell viability and reduce infarct size during the procession of AMI. Moreover, lncRNA FAF was confirmed as a sponge of miR-185-5p and promoted PAK2 expression in cardiomyocytes. Collectively, our findings reveal a novel lncRNA FAF/miR-185-5p/PAK2 axis as a crucial regulator in cardiomyocyte pyroptosis, which might be a potential therapeutic target of AMI.
细胞焦亡与多种心血管疾病相关。越来越多的证据表明，长链非编码 RNA（lncRNA）参与了基因调控，但 lncRNA 如何参与心脏细胞焦亡的调控仍知之甚少。在本研究中，我们旨在探讨 lncRNA FGF9 相关因子（FAF）在急性心肌梗死（AMI）中的抗细胞焦亡作用。检测了缺氧/缺血诱导的心肌细胞中 lncRNA FAF、miR-185-5p 和 P21 激活激酶 2（PAK2）的表达模式。通过 Hoechst 33342/PI 染色、乳酸脱氢酶（LDH）释放试验、免疫荧光和 Western blot 检测细胞焦亡。通过生物信息学分析、小 RNA 测序荧光素酶报告基因检测和 qRT-PCR 验证 lncRNA FAF、miR-185-5p 和 PAK2 之间的相互作用。lncRNA FAF 在缺氧心肌细胞和心肌组织中的表达下调。lncRNA FAF 的过表达可减轻心肌细胞焦亡，提高 AMI 过程中的细胞活力并减少梗死面积。此外，lncRNA FAF 被证实是 miR-185-5p 的海绵，并在心肌细胞中促进 PAK2 的表达。总之，我们的研究结果揭示了一个新的 lncRNA FAF/miR-185-5p/PAK2 轴作为心肌细胞焦亡的关键调节因子，可能是 AMI 的潜在治疗靶点。
