Exploring gene expression, alternative splicing events and RNA-binding proteins changes in PBMC from patients with hyperuricemia

IF 2.6 3区生物学 Q2 GENETICS & HEREDITY Gene Pub Date : 2025-01-17 DOI:10.1016/j.gene.2025.149256

Xuanxia Wu , Juan Bu , Xiaoshan Niu , Yeledan Mahan , Yanmin Zhang , Xiaoling Zhang , Abulaiti Aizezi , Xia Yu , Shengnan Zhang , Ling Zhou

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Abstract

Aim

The objective of this study was to examine the transcriptomic profile changes in hyperuricemia (HUA) and to investigate the pathogenic mechanisms and biomarkers of HUA from a transcriptomic perspective.

Methods

In this study, three patients with HUA were randomly selected and matched with three healthy controls. Six participants provided peripheral blood mononuclear cells (PBMCs) for analysis. RNA sequencing (RNA-seq) was used to identify differentially expressed genes (DEGs) and alternative splicing events (ASEs). Gene Ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to identify the functions and pathways of the DEGs and ASEs. Additionally, a co-expression network was constructed to analyze the regulation of DEGs and ASEs by RNA-binding protein (RBP) genes. In addition, important DEGs and ASEs were validated using quantitative real-time PCR (qPCR).

Results

There were 633 DEGs identified, 348 up-regulated DEGs and 285 down-regulated DEGs, including RGS18, CAVIN2, GZMH, GNLY and MT-TV, which were mainly enriched in inflammatory and immune-related biological processes. A total of 1542 ASEs were significantly differentially expressed in HUA, of which LTB4R and ENTPD4 were closely associated with the development of HUA. In addition, 15 RBP genes were detected to be differentially expressed in HUA. Three RBP genes (IFIT1, IFFIT2, and IFIT3) were highly associated with immunoinflammation and affected HUA by modulating downstream immune responses, inflammatory response-associated DEGs, and ASEs. The selected five DEGs and two ASEs were verified by qPCR, which was consistent with the results of RNA sequencing.

Conclusions

In summary, the findings indicate that HUA is associated with significant changes in inflammatory and immune response-related genes (RGS18, CAVIN2, GZMH, GNLY, MT-TV, LTB4R, ENTPD4, IFIT1, IFFIT2, and IFIT3). These findings suggest potential biomarkers and therapeutic targets.

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探索高尿酸血症患者PBMC中基因表达、选择性剪接事件和rna结合蛋白的变化。

目的：本研究的目的是研究高尿酸血症（HUA）的转录组学变化，并从转录组学的角度探讨HUA的致病机制和生物标志物。方法：本研究随机选取3例HUA患者与3例健康对照。6名参与者提供外周血单个核细胞（PBMCs）用于分析。RNA测序（RNA-seq）用于鉴定差异表达基因（DEGs）和选择性剪接事件（ase）。通过基因本体（GO）生物学过程和京都基因与基因组百科全书（KEGG）途径分析，确定了deg和ase的功能和途径。此外，构建共表达网络，分析rna结合蛋白（RBP）基因对DEGs和ase的调控作用。此外，使用定量实时PCR （qPCR）验证了重要的deg和ase。结果：共鉴定出633个蛋白，其中上调348个，下调285个，主要富集于炎症和免疫生物学过程，包括RGS18、CAVIN2、GZMH、GNLY和MT-TV。共有1542个ase在HUA中有显著差异表达，其中LTB4R和ENTPD4与HUA的发生密切相关。此外，在HUA中检测到15个RBP基因的差异表达。三个RBP基因（IFIT1、IFFIT2和IFIT3）与免疫炎症高度相关，并通过调节下游免疫反应、炎症反应相关的deg和ase来影响HUA。筛选出的5个deg和2个ase经qPCR验证，与RNA测序结果一致。结论：综上所述，研究结果表明HUA与炎症和免疫反应相关基因（RGS18、CAVIN2、GZMH、GNLY、MT-TV、LTB4R、ENTPD4、IFIT1、IFFIT2和IFIT3）的显著变化有关。这些发现提示了潜在的生物标志物和治疗靶点。

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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来源期刊

Gene 生物-遗传学

CiteScore

6.10

自引率

2.90%

发文量

718

审稿时长

42 days

期刊介绍： Gene publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses.