Bioinformatics analysis and validation of novel biomarkers and competitive endogenous RNA networks involved in

Siyu Wu1,2, Lan Yao3, Wenxiang Zhang1

  • 1College of Traditional Chinese Medicine, Xinjiang Medical University, Urumuqi, 830017, China.

Scientific Reports
|February 14, 2025
PubMed

Insights

Diabetic nephropathy (DN) involves pyroptosis, a cell death process. This study identifies key pyroptosis genes and a competing RNA network, offering potential biomarkers for DN diagnosis and treatment.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • Diabetic nephropathy (DN) is a severe complication of diabetes mellitus.
  • Pyroptosis, a form of programmed cell death, is implicated in DN pathogenesis, but its molecular mechanisms remain largely unknown.
  • Identifying reliable biomarkers and regulatory networks is crucial for understanding and managing DN.

Purpose of the Study:

  • To identify pyroptosis-related biomarkers for diabetic nephropathy (DN).
  • To elucidate the competing endogenous RNA (ceRNA) networks involved in pyroptosis during DN development.
  • To validate potential diagnostic and regulatory targets in both clinical and animal models.

Main Methods:

  • Bioinformatic analysis of Gene Expression Omnibus (GEO) datasets to identify differentially expressed pyroptosis-related genes (DEPRGs).
  • Machine learning and Receiver Operating Curve (ROC) analysis for biomarker validation.
  • Construction and validation of a ceRNA network using differentially expressed miRNAs and lncRNAs.
  • Experimental validation in a diabetic nephropathy rat model using Western blotting and qRT-PCR.

Main Results:

  • Four significantly upregulated hub DEPRGs (CASP1, TXNIP, IRF9, TRAF3) were identified and validated.
  • A pyroptosis-associated ceRNA network was constructed, highlighting potential regulatory axes in DN.
  • Immune infiltration analysis revealed significant alterations in the DN kidney microenvironment.
  • The identified ceRNA network was validated in both clinical samples and a rat model, confirming its relevance to DN.

Conclusions:

  • The study successfully identified key pyroptosis-related genes and a novel ceRNA network as potential biomarkers for diabetic nephropathy.
  • The findings suggest that this ceRNA network plays a critical role in regulating pyroptosis in DN.
  • These results provide a foundation for developing targeted diagnostic and therapeutic strategies for DN.