Background. The association between heart failure (HF) and cognitive impairment has received increasing attention from scholars and researchers in recent years. However, no systematic studies have been carried out yet focused on the crosstalk between heart failure and cognitive impairment via miRNAs. Methods. GSE104150, GSE53473, GSE120584, and GSE116250 with RNA-seq data and clinical data were downloaded from the GSE database. All data were statistically analysed using R software to detect DE-miRNAs and DE-mRNAs associated with both HF and cognitive impairment. Protein-protein interaction (PPI) networks were mapped, and a logistic regression model for cognitive impairment prediction was developed. Furthermore, the TTRUST database and miRWalk were used to map miRNA-transcription factor (TF) and messenger RNA (mRNA) regulatory pathways. Finally, core TFs were enriched for analysis. Results. Differentially enriched DE-miRNAs and DE-mRNAs both present in HF and cognitive impairment were determined. A logistic regression model established based on DE-miRNAs was validated to have a strong performance in cognitive impairment prediction. The core miRNA-TF-mRNA pathway was formed by mapping the PPI networks associated with the two diseases. Further GSEA was performed with V-rel reticuloendotheliosis viral oncogene homolog B (RELB) as the core TF, and the retinol metabolism and gap junction pathways were analysed. Conclusions. This study was the first attempt to predict the crosstalk and examine underlying mechanisms between HF and cognitive impairment applying bioinformatics. The findings suggested a potential hsa-miR-933/RELB/CCL21 regulatory axis correlated with HF and neurological disorders (or cognitive impairment), according to PPI networks.

中文翻译：

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通过 hsa-miR-933/RELB/CCL21 通路的心力衰竭和认知障碍之间的串扰

背景。近年来，心力衰竭（HF）与认知障碍之间的关联越来越受到学者和研究人员的关注。然而，尚未进行系统研究关注心力衰竭和认知障碍之间通过 miRNA 的串扰。方法. 从 GSE 数据库下载 GSE104150、GSE53473、GSE120584 和 GSE116250 以及 RNA-seq 数据和临床数据。使用 R 软件对所有数据进行统计分析，以检测与 HF 和认知障碍相关的 DE-miRNA 和 DE-mRNA。绘制了蛋白质-蛋白质相互作用 (PPI) 网络，并开发了用于预测认知障碍的逻辑回归模型。此外，TTRUST 数据库和 mirWalk 用于绘制 miRNA 转录因子 (TF) 和信使 RNA (mRNA) 调控途径。最后，丰富了核心 TF 以供分析。结果. 确定了存在于 HF 和认知障碍中的差异富集的 DE-miRNA 和 DE-mRNA。验证了基于 DE-miRNA 建立的逻辑回归模型在认知障碍预测中具有很强的性能。核心 miRNA-TF-mRNA 通路是通过绘制与这两种疾病相关的 PPI 网络形成的。以 V-rel 网状内皮增生病毒癌基因同源物 B (RELB) 作为核心 TF 进行进一步的 GSEA，并分析视黄醇代谢和间隙连接通路。结论. 本研究首次尝试应用生物信息学预测串扰并检查 HF 与认知障碍之间的潜在机制。根据 PPI 网络，研究结果表明潜在的 hsa-miR-933/RELB/CCL21 调节轴与 HF 和神经系统疾病（或认知障碍）相关。