Department of Clinical Laboratory, Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.
Kidney Blood Press Res. 2024;49(1):528-547. doi: 10.1159/000539571. Epub 2024 May 31.
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.
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.
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.
This study sheds light on a novel ceRNA regulatory network mechanism associated with autophagy in IgAN development.
IgA 肾病（IgAN）是一种全球普遍存在的肾小球疾病，其发病机制复杂，具有重要的经济意义。尽管缺乏成功的研究，本研究旨在发现 IgAN 中自噬相关基因的潜在竞争性内源 RNA（ceRNA）网络，并研究其与免疫细胞浸润的相关性。
通过评估 GSE116626 数据集并构建蛋白质-蛋白质相互作用网络，发现自噬相关的枢纽基因。使用 Neproseq 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，还构建了 ceRNA 网络，并使用 CIBERSORT 工具分析免疫细胞浸润。此外，还使用差异表达的自噬相关基因预测 IgAN 的潜在靶向药物。
总体而言，在 IgAN 中发现了 1396 个差异表达基因和 25 个自噬相关差异表达信使 RNA。富集分析表明，自噬和细胞凋亡在生物学过程中具有显著的参与。接下来，我们根据最高度评估了顶级枢纽节点。通过验证五个枢纽基因：SIRT1、FOS、CCL2、CDKN1A 和 MYC，在 GSE35487 和 GSE37460 数据集中证实了 IgAN 区分能力。在 Neproseq v5 分析引擎中，验证了五个枢纽基因的临床相关性。此外，ceRNA 网络在 IgAN 中确定了与枢纽自噬相关基因相关的 18 个环状 RNA 和 2 个 microRNA。我们的研究发现 hsa-miR-32-3p 和 hsa-let-7i-5p 表达水平升高，具有重要的诊断价值。最后，发现四个不同浸润的免疫细胞与枢纽自噬相关基因相关，并确定 67 种药物为 IgAN 的潜在治疗选择。
本研究揭示了 IgAN 发展中与自噬相关的新型 ceRNA 调控网络机制。
