Microinflammation-Driven Gene Expression Dynamics in the Pathogenesis of Metabolic Disorders and Cancer

Area of Science:

• Molecular biology
• Genomics
• Oncology

Background:

• Microinflammation is a key factor connecting metabolic diseases and cancer.
• Shared molecular mechanisms underlying these conditions remain incompletely understood.

Purpose of the Study:

• To identify common molecular drivers of inflammation-mediated pathology across metabolic diseases and cancers.
• To explore the role of RNA processing and proteostasis in these interconnected diseases.

Main Methods:

• Integration of gene expression profiles from irritable bowel syndrome (IBS), obesity, type 2 diabetes (T2D), colorectal cancer (CRC), renal cell carcinoma (RCC), and pancreatic cancer (PC).
• Weighted gene co-expression network analysis (WGCNA) to identify preserved gene modules and hub genes.
• Analysis of regulatory microRNAs (miRNAs) and their network interactions.

Main Results:

• Three highly preserved gene modules (blue, brown, turquoise) were identified, enriched in RNA processing, spliceosome assembly, ribosome biogenesis, and proteostasis.
• Key hub genes and regulatory miRNAs form interconnected networks modulating transcription, mRNA maturation, protein synthesis, and inflammatory signaling.
• Inflammation appears indirectly regulated by disruptions in RNA processing and proteostasis, potentially influenced by gut microbiota and metabolic states.

Conclusions:

• Conserved molecular signatures link microinflammation, metabolic disease, and oncogenesis.
• RNA regulation, proteostasis, and miRNA-mediated control represent potential diagnostic and therapeutic targets.