Department Cardiovascular Surgery, Xuzhou Cancer Hospital, Xuzhou City, Jiangsu, China.
Bioengineered. 2022 Apr;13(4):10786-10802. doi: 10.1080/21655979.2022.2065743.
Myocardial infarction (MI) is the leading cause of sudden death. Long non-doing RNAs (lncRNAs) were demonstrated to play crucial roles in multiple diseases, including cancer and cardiovascular diseases. Nevertheless, the molecular mechanism of lncNRAs in MI is unclear. In this study, we integrated bioinformatics and molecular biological experiments to identify the novel lncRNA transcripts and elucidated its regulatory mechanism in MI. First, we identified 10 dysregualted lncRNAs and found that lncRNA was the top risk factor in MI. Bioinformatics analysis predicted that lncRNA exerted function via targeting and was also the known regulator of ferroptosis. Inhibition or overexpression of lncRNA could regulate expression and downstream ferroptosis activity. Overexpression of could inhibit the expression of and the activity of ferroptosis, thereby attenuated cellular injury. Mechanically, co-transfection experiments showed that overexpression of could reverse the damage effect that was caused by lncRNA overexpression, via inhibiting and ferroptosis. Additionally, inhibition of lncRNA by stem cell membrane coated siRNA could attenuate MI in . Our study elucidated a novel mechanism containing lncRNA ///ferroptosis in MI, which provided a potential therapeutic for MI.Graphical Abstract. Stem cell membrane coated siRNA of lncRNA inhibits cardiomyocyte ferroptosis in myocardial infarction rat. Stem cell membrane-coated siRNA of lncRNA increases , and then suppresses the to reduce lipid peroxidation toxicity, and then inhibits cardiomyocyte ferroptosis. PUFA: polyunsaturated fatty acid.
心肌梗死（MI）是猝死的主要原因。长非编码 RNA（lncRNAs）被证明在多种疾病中发挥关键作用，包括癌症和心血管疾病。然而，lncRNAs 在 MI 中的分子机制尚不清楚。在这项研究中，我们整合了生物信息学和分子生物学实验，以鉴定新型 lncRNA 转录本，并阐明其在 MI 中的调控机制。首先，我们鉴定了 10 个失调的 lncRNAs，发现 lncRNA 是 MI 的首要危险因素。生物信息学分析预测，lncRNA 通过靶向 和 发挥作用，而 也是铁死亡的已知调节剂。lncRNA 的抑制或过表达可以调节 的表达和下游铁死亡活性。过表达 可以抑制 的表达和铁死亡的活性，从而减轻细胞损伤。机制上，共转染实验表明，过表达 可以通过抑制 和铁死亡来逆转 lncRNA 过表达引起的损伤效应。此外，干细胞膜包裹的 siRNA 抑制 lncRNA 可以减轻 中的 MI。我们的研究阐明了一个包含 lncRNA///铁死亡的 MI 新机制，为 MI 提供了一种潜在的治疗方法。
