Integrative Transcriptomics and Machine Learning Reveal the Association of CBX4 with Inflammation in Ulcerative...

Area of Science:

• Gastroenterology
• Epigenetics
• Immunology

Background:

• Epigenetic factors are implicated in intestinal diseases like ulcerative colitis (UC), but their specific roles are unclear.
• Understanding these mechanisms is crucial for developing targeted UC therapies.

Purpose of the Study:

• To identify key epigenetic factor-related genes (EFRGs) involved in UC pathogenesis.
• To investigate the role of the hub gene CBX4 in UC and its potential as a therapeutic target.

Main Methods:

• Integrated transcriptome profiles of UC patients with epigenetic factor-related genes (EFRGs).
• Utilized machine learning and Artificial Neural Network (ANN) models for gene screening and validation.
• Performed enrichment analysis, immune infiltration assays, immunohistochemistry, and in vivo knockdown experiments in a DSS-induced colitis mouse model.

Main Results:

• Identified SMARCB1, JAK2, CBX4, and PPARGC1A as key genes in UC, with CBX4 and JAK2 upregulated.
• CBX4 expression was elevated in UC patients and DSS-treated mice, correlating with disease severity.
• CBX4 knockdown ameliorated DSS-induced colon damage and inflammation in mice.

Conclusions:

• Four EFRG-related key genes (SMARCB1, JAK2, CBX4, PPARGC1A) were identified in UC.
• CBX4 acts as a significant epigenetic regulator in UC pathogenesis.
• Targeting CBX4 shows promise for developing novel therapeutic strategies for ulcerative colitis.