Integrated Bioinformatics and Experimental Validation Reveal Shared Molecular Targets for Diagnosis and Intervention in Type 2 Diabetes Mellitus and Diabetic Nephropathy

作者：Syed Shah Zaman Haider Naqvi, Zhitong Li, Ruixue Duan, Jiaojiao Li, Wenxia Ren, Muhammad Zaeem, Shoaib Muhammad, Imran Ali, Shiwei Liu · 发表于：Current Molecular Medicine · 年份：2026 · DOI：10.2174/0115665240446197260120100411 · 研究领域：Chronic Kidney Disease and Diabetes、Bioinformatics and Genomic Networks、Ferroptosis and cancer prognosis

Introduction: Type 2 diabetes mellitus (T2DM) is a major risk factor for diabetic nephropathy (DN), yet the molecular mechanisms connecting these conditions remain unclear. Identifying shared hub genes and regulatory networks may provide insight into common pathogenic pathways. Methods: Four GEO microarray datasets associated with T2DM (GSE23343, GSE29226) and DN (GSE30528, GSE142153) were analyzed using limma in R to identify differentially expressed genes (DEGs). Overlapping DEGs were assessed using Venn analysis and integrated into a STRING-based protein–protein interaction network. Hub genes were identified in Cytoscape. Their expression under high-glucose conditions was validated in HK-2 and NRK-52E cells using RT-qPCR and Western blotting. Predicted miRNAs were obtained from TargetScan and evaluated experimentally. Functional assays assessed the effects of hub gene overexpression. Results: Thirty-six common DEGs were identified, with APP, RHEB, FRYL, and SOS1 exhibiting highest network connectivity. All four genes were consistently downregulated in patient datasets and high-glucose cell models. ROC analyses indicated moderate discriminatory capacity within datasets. Four candidate miRNAs (miR-26b-5p, miR-18a-5p, miR-199a-5p, miR-148a-3p) were elevated under highglucose conditions. Functional enrichment linked hub genes to mTOR, PI3K–Akt, and cytoskeletal pathways. Overexpression of hub genes reduced proliferation, clonogenicity, and migration in vitro. Results: Thirty-s...