Abstract：
In this study, we identified FOXP3 as a transcription factor for lncRNA SNHG1, which exerts a significant protective role against cardiomyocyte hypertrophy. Through DNA-pull down experiments and ChIP analysis, we confirmed that FOXP3 could bind to the promoter of SNHG1. Luciferase reporter and RT-qPCR experiments validated that FOXP3 overexpression promoted SNHG1 expression in cardiomyocytes. Furthermore, in a model of cardiomyocyte hypertrophy, FOXP3 expression was upregulated, particularly in cardiomyocytes. Functional assays demonstrated that FOXP3 overexpression inhibited cardiomyocyte hypertrophy, while FOXP3 knockdown held the opposite effect. Additionally, we revealed that lncRNA SNHG1 acted as a sponge for miR-182, miR-326, and miR-3918, thereby stabilizing FOXP3 mRNA in cardiomyocytes. The protective role of SNHG1 against cardiomyocyte hypertrophy was found to depend on the presence of FOXP3, forming a positive FOXP3/SNHG1 feedback axis. Moreover, we unveiled this positive FOXP3/SNHG1 feedback axis suppressed cardiomyocyte hypertrophy by negatively regulating Parkin-mediated mitophagy. These findings provide novel insights into the molecular mechanisms underlying cardiomyocyte hypertrophy and offer potential therapeutic targets for related interventions.
摘要：
在这项研究中,我们将FOXP3鉴定为lncRNASNHG1的转录因子,它对心肌细胞肥大具有显著的保护作用.通过DNA下拉实验和ChIP分析,我们证实FOXP3可以与SNHG1的启动子结合。荧光素酶报告基因和RT-qPCR实验证实FOXP3过表达促进心肌细胞中的SNHG1表达。此外，在心肌细胞肥大的模型中，FOXP3表达上调,特别是在心肌细胞中。功能实验证明FOXP3过表达抑制心肌细胞肥大,而FOXP3敲低则起到相反的作用。此外,我们发现，lncRNASNHG1充当miR-182，miR-326和miR-3918的海绵，从而稳定心肌细胞中的FOXP3mRNA。发现SNHG1对心肌细胞肥大的保护作用取决于FOXP3的存在，形成FOXP3/SNHG1正反馈轴。此外，我们揭示了这种阳性FOXP3/SNHG1反馈轴通过负调节Parkin介导的线粒体自噬抑制心肌细胞肥大.这些发现为心肌细胞肥大的分子机制提供了新的见解，并为相关干预措施提供了潜在的治疗靶点。
