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Integrated Bioinformatics and Experimental Validation Reveal Shared Molecular Targets for Diagnosis and Intervention

Syed Shah Zaman Haider Naqvi1, Zhitong Li1, Ruixue Duan1

  • 1Department of Endocrinology, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, Shanxi Province, P.R. China.

Current Molecular Medicine
|July 28, 2026
PubMed
Abstract

Insights

Reduced expression of key genes like APP and RHEB may link type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). These findings offer potential therapeutic targets for T2DM and DN.

Area of Science:

  • Genomics and Molecular Biology
  • Diabetology and Nephrology

Background:

  • Type 2 diabetes mellitus (T2DM) is a significant risk factor for diabetic nephropathy (DN).
  • The precise molecular mechanisms linking T2DM and DN are not fully understood.
  • Identifying shared molecular pathways could illuminate common pathogenic mechanisms.

Purpose of the Study:

  • To identify shared hub genes and regulatory networks between T2DM and DN.
  • To investigate the functional roles of these shared genes in disease pathogenesis.
  • To explore potential molecular targets for T2DM and DN.

Main Methods:

  • Analysis of four Gene Expression Omnibus (GEO) microarray datasets for T2DM and DN.
  • Identification of differentially expressed genes (DEGs) using limma.
  • Construction of protein-protein interaction networks and identification of hub genes using STRING and Cytoscape.
  • Experimental validation of hub gene expression and miRNA associations in cell models.
  • Functional assays to assess the impact of hub gene overexpression.

Main Results:

  • Thirty-six common DEGs were identified between T2DM and DN datasets.
  • APP, RHEB, FRYL, and SOS1 emerged as high-connectivity hub genes, consistently downregulated.
  • Candidate miRNAs (miR-26b-5p, miR-18a-5p, miR-199a-5p, miR-148a-3p) were elevated under high-glucose conditions.
  • Hub gene overexpression in vitro reduced cell proliferation, clonogenicity, and migration.

Conclusions:

  • Downregulation of hub genes APP, RHEB, FRYL, and SOS1 may contribute to glucose-induced cellular dysfunction in T2DM and DN.
  • These genes represent shared molecular signatures for T2DM and DN.
  • Further validation of miRNA-gene relationships and studies in diverse cell types and patient cohorts are warranted.
Keywords:
BiomarkerDiabetic nephropathyHub geneTreatment.Type 2 diabetes mellitusmiRNA

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