Bioinformatics analysis reveals shared molecular pathways for relationship between ulcerative colitis and primary...

Area of Science:

• Gastroenterology
• Hepatology
• Molecular Biology

Background:

• Inflammatory bowel disease (IBD), encompassing ulcerative colitis (UC) and Crohn's disease, causes chronic gastrointestinal inflammation and significant morbidity.
• Extraintestinal manifestations of IBD, such as primary sclerosing cholangitis (PSC), can precede IBD diagnosis and lead to liver cirrhosis and cholangiocarcinoma.
• PSC is a progressive cholestatic liver disease strongly associated with UC, necessitating research into their shared molecular underpinnings.

Purpose of the Study:

• To identify molecular contributors and differentially expressed genes (DEGs) common to both ulcerative colitis (UC) and primary sclerosing cholangitis (PSC).
• To construct gene regulatory networks, including miRNA and circRNA interactions, for UC-PSC.
• To discover potential therapeutic targets and diagnostic tools for UC-associated PSC.

Main Methods:

• Utilized DisGeNET and GEO databases to identify shared single-nucleotide polymorphisms (SNPs) and DEGs between UC and PSC.
• Constructed protein-protein interaction (PPI) and co-expression networks to identify hub genes.
• Built a competing endogenous RNA (ceRNA) network using miRNA and circRNA data.

Main Results:

• Identified 132 shared SNPs and 56 common DEGs between UC and PSC.
• The PTPN2 gene was the sole gene common at both SNP and expression levels.
• Functional enrichment analysis highlighted mRNA splicing and RNA binding processes; a ceRNA network of 4 mRNAs, 94 miRNAs, and 200 circRNAs was constructed.

Conclusions:

• Identified novel candidate genes and molecular pathways linking UC and PSC.
• These findings provide a basis for developing diagnostic biomarkers and therapeutic strategies.
• The study aims to prevent the progression of PSC in patients with UC.