ANKRD46 as a shared diagnostic and therapeutic marker in keloid and type 2 diabetes mellitus identified via multi

Tingting Yu1, Fang Liu2, Yiyi Gong2

  • 1Department of Dermatology, Pudong New Area People's Hospital, Shanghai, China.

Abstract

Insights

Keloids and Type 2 diabetes share inflammation and healing issues. ANKRD46 is identified as a key diagnostic marker and potential therapeutic target for both conditions.

Area of Science:

  • Biomedical Science
  • Molecular Biology
  • Genomics

Background:

  • Keloids and Type 2 diabetes mellitus (T2DM) are characterized by chronic inflammation and impaired wound healing.
  • Investigating molecular commonalities may uncover shared therapeutic targets for these distinct conditions.

Purpose of the Study:

  • To identify shared molecular mechanisms and diagnostic biomarkers between keloids and T2DM.
  • To explore ANKRD46 as a potential therapeutic target.

Main Methods:

  • Multi-omics analysis of RNA expression data from keloid and T2DM samples.
  • Differential gene expression analysis, Weighted Gene Co-expression Network Analysis (WGCNA), and machine learning (LASSO, SVM-RFE) were employed.
  • Experimental validation included Western blotting, qRT-PCR, IHC, flow cytometry, and mouse models.

Main Results:

  • Twenty differentially expressed genes (DEGs) overlapped between keloids and T2DM, enriched in glucose metabolism and immune response pathways.
  • ANKRD46 was identified as a robust diagnostic marker, correlating with immune cells like plasmacytoid dendritic cells and activated B cells.
  • ANKRD46 upregulation was confirmed experimentally, with diagnostic models showing AUC > 0.75. Its association with the IL6-JAK-STAT3 pathway and regulation by miR-21 was established.

Conclusions:

  • ANKRD46 serves as a promising shared diagnostic and therapeutic target for keloids and T2DM.
  • ANKRD46's role in immune response and fibrosis regulation, particularly via the IL6-JAK-STAT3 pathway, is supported by computational and experimental evidence.
  • This study provides a basis for developing novel therapeutic strategies targeting ANKRD46 for both keloids and T2DM.