Department of Clinical Laboratory Medicine, Ziyang Central Hospital, Ziyang, 641300, Sichuan Province, China.
Department of Infectious Disease, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Child Rare Diseases in Infection and Immunity, Children's Hospital of Chongqing Medical University, Chongqing, 401122, China.
Sci Rep. 2024 Nov 28;14(1):29577. doi: 10.1038/s41598-024-81080-z.
Heart failure (HF) is the leading cause of death in patients with maintenance hemodialysis (MHD). Biomarkers has an important guiding role in the early diagnosis, risk stratification, and prognostic assessment of HF. Increasing studies have indicated that long non-coding RNAs (lncRNAs) have played an indispensable role in the regulatory network of HF. This study was aiming to explore the expression profiles of lncRNAs in patients treated with MHD developing heart failure. Peripheral blood mononuclear cells were isolated from 4 hemodialysis patients with reduced ejection fraction (HFrEF) and 4 hemodialysis patients with preserved ejection fraction (HFpEF), respectively. The expression profile analysis of lncRNAs was performed by using Illumina Novaseq 6000 sequencer. Quantitative real time polymerase chain reaction (qRT-PCR) was used to verify the expression of representative differentially expressed lncRNAs. Based on lncRNA-miRNA-mRNA-KEGG network analysis, the potential role of candidate lncRNAs and their association with the severity of HF were further evaluated. In total, 1,429 differentially expressed lncRNAs were found between patients with HFrEF and patients with HFpEF, of which 613 were up-regulated and 816 were down-regulated (P < 0.05). Five candidate lncRNAs were screened out by a series of bioinformatic analyses. After being compared with miRBase, ENST00000561762, one of the 5 candidates, was considered the most likely lncRNA to be serving as a precursor for miRNA. Nine predicted target genes were found by further lncRNA-miRNA-mRNA-KEGG network analysis, and among which ITGB5 was enriched in the actin dynamics signaling pathway. In another cohort of hemodialysis patients, the expression of lncRNA ENST00000561762 was verified by qRT-PCR. Further analysis revealed that there was a strong correlation between left ventricular ejection fraction and ENST00000561762, proBNP, and 6-minute walk distance, respectively. LncRNAs expression profile was remarkably different in hemodialysis patients with HFrEF compared to those with HFpEF. Among which, lncRNA ENST00000561762 was considered as a promising biomarker for patients with HFrEF as it was predicted to be a miRNA precursor to regulate the actin dynamics signaling pathway.
心力衰竭（HF）是维持性血液透析（MHD）患者死亡的主要原因。生物标志物在 HF 的早期诊断、风险分层和预后评估中具有重要的指导作用。越来越多的研究表明，长非编码 RNA（lncRNA）在 HF 的调控网络中发挥了不可或缺的作用。本研究旨在探讨 MHD 合并心力衰竭患者外周血单个核细胞 lncRNA 的表达谱。分别从 4 例射血分数降低的心力衰竭（HFrEF）患者和 4 例射血分数保留的心力衰竭（HFpEF）患者中分离外周血单个核细胞。采用 Illumina Novaseq 6000 测序仪进行 lncRNA 表达谱分析。采用实时定量聚合酶链反应（qRT-PCR）验证代表性差异表达 lncRNA 的表达。基于 lncRNA-miRNA-mRNA-KEGG 网络分析，进一步评估候选 lncRNA 的潜在作用及其与 HF 严重程度的关系。共发现 HFrEF 患者与 HFpEF 患者之间存在 1429 个差异表达的 lncRNA，其中 613 个上调，816 个下调（P<0.05）。通过一系列生物信息学分析筛选出 5 个候选 lncRNA。与 miRBase 比较后，认为 5 个候选物之一的 ENST00000561762 最有可能作为 miRNA 的前体。通过进一步的 lncRNA-miRNA-mRNA-KEGG 网络分析，发现了 9 个预测的靶基因，其中 ITGB5 富集在肌动蛋白动力学信号通路中。在另一组血液透析患者中，通过 qRT-PCR 验证了 lncRNA ENST00000561762 的表达。进一步分析表明，左心室射血分数与 ENST00000561762、proBNP 和 6 分钟步行距离分别呈强相关。与 HFpEF 患者相比，HFrEF 患者的 lncRNA 表达谱差异显著。其中，lncRNA ENST00000561762 被认为是 HFrEF 患者有前途的生物标志物，因为它被预测为调节肌动蛋白动力学信号通路的 miRNA 前体。
