Differential expressions of exosomal miRNAs in patients with chronic heart failure and hyperuricemia: diagnostic values of miR-27a-5p and miR-139-3p.

Q3 Medicine

南方医科大学学报杂志 Pub Date : 2025-01-20 DOI:10.12122/j.issn.1673-4254.2025.01.06

Zhiliang Chen, Yonggang Yang, Xia Huang, Yan Cheng, Yuan Qu, Qiqi Heng, Yujia Fu, Kewei Li, Ning Gu

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引用次数: 0

Abstract

Objectives: To analyze the differentially expressed exosomal miRNAs in patients with chronic heart failure (CHF) complicated by hyperuricemia (HUA) and explore their potential as novel diagnostic molecular markers and their target genes.

Methods: This study was conducted among 30 CHF patients with HUA (observation group) and 30 healthy volunteers (control group) enrolled between September, 2020 and September, 2023. Peripheral blood samples were collected from 6 CHF patients with HUA for analyzing exosomal miRNAs by high-throughput sequencing, and the results were validated in the remaining 24 patients using qRT-PCR. GO and KEGG enrichment analyses were performed to predict the the target genes of the identified differential miRNAs. We also validated the differentially expressed miRNAs by animal experiment.

Results: A total of 42 differentially expressed exosomal miRNAs were detected in observation group by high-throughput sequencing; among them, miR-27a-5p was significantly upregulated (P=0.000179), and miR-139-3p was significantly downregulated (P=0.000058). In the 24 patients with both CHF and PUA, qRT-PCR validated significant upregulation of miR-27a-5p (P=0.004) and downregulation of miR-139-3p (P=0.005) in serum exosomes. When combined, miR-27a-5p and miR-139-3p had a maximum area under the curve (AUC) of 0.899 (95% CI: 0812-0.987) for predicting CHF complicated by HUA. GO and KEGG enrichment analyses suggested that the differential expressions of miR-27a-5p and miR-139-3p was associated with the activation of the AMPK-mTOR signaling pathway to activate the autophagic response. We obtained the same conclusion from animal experiment.

Conclusions: Upregulated exosomal miR-27a-5p combined with downregulated exosomal miR-139-3p expression can serve as a novel molecular marker for diagnosis of CHF complicated by HUA, and their differential expression may promote autophagy in cardiomyocytes by activating the AMPK-mTOR signaling pathway.

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慢性心力衰竭和高尿酸血症患者外泌体mirna的差异表达：miR-27a-5p和miR-139-3p的诊断价值

目的：分析慢性心力衰竭（CHF）合并高尿酸血症（HUA）患者外泌体mirna的差异表达，探讨其作为新型诊断分子标记及其靶基因的潜力。方法：本研究于2020年9月至2023年9月招募30名CHF合并HUA患者（观察组）和30名健康志愿者（对照组）。收集6例伴有HUA的CHF患者外周血样本，通过高通量测序分析外泌体mirna，并在其余24例患者中使用qRT-PCR验证结果。进行GO和KEGG富集分析以预测鉴定的差异mirna的靶基因。我们还通过动物实验验证了差异表达的mirna。结果：观察组通过高通量测序共检测到42个差异表达的外泌体mirna；其中miR-27a-5p显著上调（P=0.000179）， miR-139-3p显著下调（P=0.000058）。在24例CHF和PUA患者中，qRT-PCR证实血清外泌体中miR-27a-5p显著上调（P=0.004）， miR-139-3p显著下调（P=0.005）。联合使用miR-27a-5p和miR-139-3p预测CHF合并HUA的最大曲线下面积（AUC）为0.899 （95% CI: 0812-0.987）。GO和KEGG富集分析表明，miR-27a-5p和miR-139-3p的差异表达与AMPK-mTOR信号通路激活激活自噬反应有关。我们从动物实验中得到了同样的结论。结论：外泌体miR-27a-5p上调联合外泌体miR-139-3p下调可作为诊断CHF合并HUA的新分子标志物，其差异表达可能通过激活AMPK-mTOR信号通路促进心肌细胞自噬。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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