HMGCS2 and AMACR as potential targets linking mitochondrial dysfunction and ulcerative colitis.

Area of Science:

• Gastroenterology and Molecular Biology
• Mitochondrial Biology
• Inflammatory Bowel Disease Research

Background:

• Ulcerative colitis (UC) involves disrupted intestinal mucosal homeostasis, with mitochondrial dysfunction implicated but not fully understood.
• Further research is needed to elucidate the specific roles of mitochondria in UC pathogenesis.

Purpose of the Study:

• To identify novel mitochondria-related genes (MitoDEGs) associated with UC.
• To investigate the diagnostic value and functional impact of these genes in UC.

Main Methods:

• Differential gene expression analysis of the GSE87466 dataset.
• Utilized Weighted Gene Co-expression Network Analysis (WGCNA) to identify hub genes.
• Integrated gene expression data with mitochondria-related genes from MitoCart3.0 and applied machine learning algorithms.

Main Results:

• Identified 14 MitoDEGs, with HMGCS2 and AMACR selected as key signature genes for UC.
• HMGCS2 and AMACR exhibit decreased expression in UC patients and possess high diagnostic value.
• Knockout of HMGCS2 and AMACR impaired mitochondrial structure and function in an inflammatory setting, with AMACR knockdown notably affecting mitochondria and MAMs.

Conclusions:

• HMGCS2 and AMACR are identified as novel signature MitoDEGs in UC.
• These genes offer insights into the relationship between mitochondrial dysfunction and intestinal mucosal homeostasis in UC.
• HMGCS2 and AMACR represent potential therapeutic targets and diagnostic biomarkers for UC.