Deng Haihong, Fan Qisen, Huang Lichao, Ouyang Wenbo, Zhu Wendian
Department of Anesthesiology, The First People's Hospital of Zhaoqing, Zhaoqing City, Guangdong Province, People's Republic of China.
Department of Anesthesiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou City, Guangdong Province, People's Republic of China.
J Inflamm Res. 2025 Jan 22;18:1033-1051. doi: 10.2147/JIR.S485348. eCollection 2025.
Myocardial ischemia/reperfusion (I/R) injury significantly impacts the recovery of ischemic heart disease patients. Non-coding RNAs, including miRNAs, have been increasingly recognized for their roles in regulating cardiomyocyte responses to hypoxia/reoxygenation (H/R) injury. miR-181c-5p, in particular, has been implicated in inflammatory and apoptotic processes, suggesting its potential involvement in exacerbating cellular damage.
This study combined bioinformatic and experimental techniques to investigate myocardial injury. Gene expression data from the GEO database were analyzed, and HL-1 cardiomyocytes were used in a hypoxia/reoxygenation model to mimic reperfusion injury. Various molecular techniques have been applied to explore the underlying mechanisms, while statistical analyses have identified potential biomarkers and therapeutic targets.
This study revealed significant upregulation of miR-181c-5p in cardiomyocyte H/R injury models, which inversely affected PTPN4 expression and activated the TLR4/NF-κB signaling pathway. Overexpression of PTPN4 inhibited this pathway. Notably, circ_0001084 was identified as absorbing miR-181c-5p, reducing its interaction with PTPN4 and subsequent pathway activation. This suggests a novel therapeutic pathway for myocardial I/R injury treatment, highlighting the interplay between non-coding RNAs and cellular stress responses.
circ_0001084 acts as a competing endogenous RNA for miR-181c-5p, enhancing PTPN4 expression and inhibiting the TLR4/NF-κB signaling pathway. These findings offer insights into the molecular mechanisms of myocardial I/R injury and potential therapeutic targets in ischemic heart disease.
心肌缺血/再灌注（I/R）损伤对缺血性心脏病患者的恢复有重大影响。包括微小RNA（miRNA）在内的非编码RNA在调节心肌细胞对缺氧/复氧（H/R）损伤的反应中的作用日益受到认可。特别是miR-181c-5p已被证明与炎症和凋亡过程有关，提示其可能参与加剧细胞损伤。
本研究结合生物信息学和实验技术来研究心肌损伤。分析了来自基因表达综合数据库（GEO数据库）的基因表达数据，并在缺氧/复氧模型中使用HL-1心肌细胞来模拟再灌注损伤。应用了各种分子技术来探索潜在机制，同时通过统计分析确定了潜在的生物标志物和治疗靶点。
本研究揭示了在心肌细胞H/R损伤模型中miR-181c-5p显著上调，这反过来影响蛋白酪氨酸磷酸酶非受体型4（PTPN4）的表达并激活Toll样受体4（TLR4）/核因子κB（NF-κB）信号通路。PTPN4的过表达抑制了该信号通路。值得注意的是，环状RNA_0001084（circ_0001084）被确定为可吸附miR-181c-5p，减少其与PTPN4的相互作用及随后的信号通路激活。这提示了一种用于治疗心肌I/R损伤的新治疗途径，突显了非编码RNA与细胞应激反应之间的相互作用。
circ_0001084作为miR-181c-5p的竞争性内源性RNA，增强PTPN4表达并抑制TLR4/NF-κB信号通路。这些发现为心肌I/R损伤的分子机制以及缺血性心脏病潜在的治疗靶点提供了见解。
