Tianjin Key Laboratory of Exercise Physiology and Sports Medicine, Tianjin University of Sport, Tianjin, China.
PLoS One. 2024 Mar 28;19(3):e0297848. doi: 10.1371/journal.pone.0297848. eCollection 2024.
Diabetic cardiomyopathy (DCM) is a major factor in the development of heart failure. Mitochondria play a crucial role in regulating insulin resistance, oxidative stress, and inflammation, which affect the progression of DCM. Regular exercise can induce altered non-coding RNA (ncRNA) expression, which subsequently affects gene expression and protein function. The mechanism of exercise-induced mitochondrial-related non-coding RNA network in the regulation of DCM remains unclear. This study seeks to construct an innovative exercise-induced mitochondrial-related ncRNA network. Bioinformatic analysis of RNA sequencing data from an exercise rat model identified 144 differentially expressed long non-coding RNA (lncRNA) with cutoff criteria of p< 0.05 and fold change ≥1.0. GSE6880 and GSE4745 were the differentially expressed mRNAs from the left ventricle of DCM rat that downloaded from the GEO database. Combined with the differentially expressed mRNA and MitoCarta 3.0 dataset, the mitochondrial located gene Pdk4 was identified as a target gene. The miRNA prediction analysis using miRanda and TargetScan confirmed that 5 miRNAs have potential to interact with the 144 lncRNA. The novel lncRNA-miRNA-Pdk4 network was constructed for the first time. According to the functional protein association network, the newly created exercise-induced ncRNA network may serve as a promising diagnostic marker and therapeutic target, providing a fresh perspective to understand the molecular mechanism of different exercise types for the prevention and treatment of diabetic cardiomyopathy.
糖尿病心肌病(DCM)是心力衰竭发展的主要因素。线粒体在调节胰岛素抵抗、氧化应激和炎症方面起着至关重要的作用,这些因素影响 DCM 的进展。有规律的运动可以诱导非编码 RNA(ncRNA)表达的改变,进而影响基因表达和蛋白质功能。运动诱导的与线粒体相关的非编码 RNA 网络在调节 DCM 中的机制尚不清楚。本研究旨在构建一种创新的运动诱导的与线粒体相关的 ncRNA 网络。对运动大鼠模型的 RNA 测序数据进行生物信息学分析,确定了 144 个差异表达的长非编码 RNA(lncRNA),其截止标准为 p<0.05,倍数变化≥1.0。从 GEO 数据库下载的 DCM 大鼠左心室的差异表达 mRNA 为 GSE6880 和 GSE4745。与差异表达 mRNA 和 MitoCarta 3.0 数据集相结合,鉴定出位于线粒体的 Pdk4 基因作为靶基因。使用 miRanda 和 TargetScan 进行 miRNA 预测分析,证实了 5 个 miRNA 可能与 144 个 lncRNA 相互作用。首次构建了新的 lncRNA-miRNA-Pdk4 网络。根据功能蛋白关联网络,新创建的运动诱导的 ncRNA 网络可能作为有前途的诊断标志物和治疗靶点,为了解不同运动类型预防和治疗糖尿病心肌病的分子机制提供了新的视角。