Integrated Bioinformatics and Structural Assessment Suggest Doxycycline as a Potential Candidate Targeting MMP7 in...

Area of Science:

• Biomedical research
• Bioinformatics
• Translational medicine

Background:

• Lung cancer (LC) and systemic sclerosis-associated interstitial lung disease (SSc-ILD) are significant health concerns with high mortality.
• While shared molecular mechanisms are suspected, the genetic overlap between LC and SSc-ILD is not well understood.

Purpose of the Study:

• To identify common differentially expressed genes (DEGs) and regulatory networks linking LC and SSc-ILD using integrative bioinformatics.
• To explore potential therapeutic strategies by investigating shared molecular pathways and drug candidates.

Main Methods:

• Comparative transcriptomic analysis to identify shared DEGs between LC and SSc-ILD.
• Regulatory network analysis to pinpoint key microRNAs (miRNAs) and transcription factors.
• Pathway enrichment analysis to determine common biological pathways.
• Molecular docking and experimental validation for drug repurposing potential.

Main Results:

• Identified 72 shared DEGs, including 10 hub genes (e.g., MMP7, CXCL14, CXCR2).
• Revealed key regulatory miRNAs (hsa-miR-34a-5p, hsa-miR-126-3p, hsa-miR-335-5p) and transcription factors (FOS, JUN, NFKB1).
• Highlighted interleukin-10 signaling as a critical shared pathway involved in immune regulation and extracellular matrix remodeling.
• Doxycycline showed potential interaction with MMP7 and antibacterial activity.

Conclusions:

• The study provides preliminary insights into the shared molecular features of LC and SSc-ILD.
• Doxycycline is proposed as a potential repurposed drug candidate for these conditions, warranting further investigation.