Fuwai Hospital, Chinese Academy of Medical Sciences, State Key Laboratory of Cardiovascular Disease, Peking Union Medical College, No.167 Beilishi Road, Xicheng District, Beijing, 100037, China.
Mol Biotechnol. 2022 Aug;64(8):902-913. doi: 10.1007/s12033-022-00471-7. Epub 2022 Feb 28.
Acute myocardial infarction (AMI) is a severe and even fatal cardiovascular disease. The effect of transcription factors on AMI is intensively explored. Our experiment attempts to probe the role of Sox9 in cardiomyocyte apoptosis after AMI. AMI cell model was established in AC16 cells by hypoxia treatment. Cell viability and apoptosis were assessed. Then, the levels of BAX, Bcl-2, Sox9, miR-223-3p, and MEF2C were detected. The binding relation between Sox9 and miR-223-3p and between miR-223-3p and MEF2C was verified. The expression of miR-223-3p was upregulated using the miR-223-3p mimic, and collaborative experiments were conducted as si-Sox9 or si-MEF2C was transfected into cells to inhibit the expression of Sox9 or MEF2C. Sox9 was highly expressed in cardiomyocyte apoptosis after hypoxia, while Sox9 silencing protected hypoxia-treated cardiomyocytes from apoptosis by enhancing cell viability, quenching apoptosis, and reducing activity of caspase-3 and caspase-9. Essentially, Sox9 bound to the miR-223-3p promoter region to upregulate its expression. miR-223-3p targeted MEF2C transcription. miR-223-3p overexpression and MEF2C silencing could counteract the suppressive role of Sox9 silencing in hypoxia-treated cardiomyocyte apoptosis. Sox9 exacerbated hypoxia-induced cardiomyocyte apoptosis by promoting miR-223-3p expression and inhibiting MEF2C transcription.
急性心肌梗死（AMI）是一种严重甚至致命的心血管疾病。转录因子对 AMI 的影响正在被深入研究。我们的实验试图探讨 Sox9 在 AMI 后心肌细胞凋亡中的作用。通过低氧处理建立 AC16 细胞的 AMI 细胞模型，评估细胞活力和凋亡。然后检测 BAX、Bcl-2、Sox9、miR-223-3p 和 MEF2C 的水平。验证 Sox9 与 miR-223-3p 之间以及 miR-223-3p 与 MEF2C 之间的结合关系。使用 miR-223-3p 模拟物上调 miR-223-3p 的表达，并转染 si-Sox9 或 si-MEF2C 以抑制 Sox9 或 MEF2C 的表达进行协同实验。低氧后心肌细胞凋亡中 Sox9 高表达，而 Sox9 沉默通过增强细胞活力、抑制凋亡和降低 caspase-3 和 caspase-9 的活性来保护低氧处理的心肌细胞免于凋亡。本质上，Sox9 与 miR-223-3p 启动子区域结合以上调其表达。miR-223-3p 靶向 MEF2C 转录。miR-223-3p 过表达和 MEF2C 沉默可以抵消 Sox9 沉默对低氧处理的心肌细胞凋亡的抑制作用。Sox9 通过促进 miR-223-3p 表达和抑制 MEF2C 转录来加剧低氧诱导的心肌细胞凋亡。
