Comprehensive Analysis of ceRNA Network and Immune Cell Infiltration Pattern of Autophagy-Related Genes in IgA Nephropathy.

IF 2.3 4区医学 Q2 PERIPHERAL VASCULAR DISEASE Kidney & blood pressure research Pub Date : 2024-01-01 Epub Date: 2024-05-31 DOI:10.1159/000539571

Huaying Zhang, Huiai Lu, Bicui Zhan, He Shi, Bingjie Shui

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Abstract

Introduction: IgA nephropathy (IgAN) is a prevalent worldwide glomerular disease with a complex pathophysiology that has significant economic implications. Despite the lack of successful research, this study aims to discover the potential competing endogenous RNA (ceRNA) network of autophagy-associated genes in IgAN and examine their correlation with immune cell infiltration.

Methods: Autophagy-related hub genes were discovered by assessing the GSE116626 dataset and constructing a protein-protein interaction network. Nephroseq v5 analysis engine was used to analyze correlations between hub genes and proteinuria, glomerular filtration rate (GFR), and serum creatinine levels. Then, a ceRNA network construction and the CIBERSORT tool for immune cell infiltration analysis were also performed. Additionally, the differentially expressed autophagy-related genes were used to predict potential targeted medications for IgAN.

Results: Overall, 1,396 differentially expressed genes were identified in IgAN along with 25 autophagy-related differentially expressed messenger RNAs. Enrichment analysis revealed significant involvement of autophagy and apoptosis in biological processes. Next, we evaluated the top hub nodes based on their highest degrees. The ability of IgAN discrimination was confirmed in the GSE35487 and GSE37460 datasets by validating the five hub genes: SIRT1, FOS, CCL2, CDKN1A, and MYC. In the Nephroseq v5 analysis engine, the clinical correlation of the five hub genes was confirmed. Furthermore, the ceRNA network identified 18 circular RNAs and 2 microRNAs associated with hub autophagy-related genes in IgAN. Our investigation identified hsa-miR-32-3p and hsa-let-7i-5p as having elevated expression levels and substantial diagnostic value. Finally, four distinctively infiltrated immune cells were found to be associated with the hub autophagy-related genes, and 67 drugs were identified as potential therapeutic options for IgAN.

Conclusion: This study sheds light on a novel ceRNA regulatory network mechanism associated with autophagy in IgAN development.

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全面分析 IgA 肾病中自噬相关基因的 ceRNA 网络和免疫细胞浸润模式

导言：IgA肾病（IgAN）是一种全球流行的肾小球疾病，其病理生理学十分复杂，具有重大的经济影响。尽管缺乏成功的研究，但本研究旨在发现 IgAN 中自噬相关基因的潜在竞争性内源性 RNA（ceRNA）网络，并研究它们与免疫细胞浸润的相关性：方法：通过评估 GSE116626 数据集和构建蛋白质-蛋白质相互作用网络，发现自噬相关的枢纽基因。使用Nephroseq v5分析引擎分析枢纽基因与蛋白尿、肾小球滤过率（GFR）和血清肌酐水平之间的相关性。然后，还进行了 ceRNA 网络构建和用于免疫细胞浸润分析的 CIBERSORT 工具。此外，还利用差异表达的自噬相关基因（DEARGs）来预测治疗IgAN的潜在靶向药物：结果：在 IgAN 中发现了 1396 个差异表达基因 (DEG)，以及 25 个与自噬相关的差异表达信使 RNA (DEmRNA)。富集分析表明，自噬和细胞凋亡在生物过程中有重要参与。接下来，我们根据最高度评估了顶级中心节点。在 GSE35487 和 GSE37460 数据集中，通过验证五个枢纽基因，确认了 IgAN 的鉴别能力：SIRT1、FOS、CCL2、CDKN1A 和 MYC。在 Nephroseq v5 分析引擎中，这五个中心基因的临床相关性得到了证实。此外，ceRNA网络还发现了18个环状RNA和2个microRNA与IgAN中的自噬相关中枢基因有关。我们的研究发现，hsa-miR-32-3p 和 hsa-let-7i-5p 具有较高的表达水平，具有重要的诊断价值。最后，我们发现四种明显浸润的免疫细胞与中枢自噬相关基因有关，并确定了 67 种药物作为 IgAN 的潜在治疗方案：本研究揭示了在 IgAN 发病过程中与自噬相关的新型 ceRNA 调控网络机制。

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

Kidney & blood pressure research 医学-泌尿学与肾脏学

CiteScore

4.80

自引率

3.60%

发文量

审稿时长

6-12 weeks

期刊介绍： This journal comprises both clinical and basic studies at the interface of nephrology, hypertension and cardiovascular research. The topics to be covered include the structural organization and biochemistry of the normal and diseased kidney, the molecular biology of transporters, the physiology and pathophysiology of glomerular filtration and tubular transport, endothelial and vascular smooth muscle cell function and blood pressure control, as well as water, electrolyte and mineral metabolism. Also discussed are the (patho)physiology and (patho) biochemistry of renal hormones, the molecular biology, genetics and clinical course of renal disease and hypertension, the renal elimination, action and clinical use of drugs, as well as dialysis and transplantation. Featuring peer-reviewed original papers, editorials translating basic science into patient-oriented research and disease, in depth reviews, and regular special topic sections, ''Kidney & Blood Pressure Research'' is an important source of information for researchers in nephrology and cardiovascular medicine.