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Transcriptome Profiling Associated with CARD11 Overexpression in Colorectal Cancer Implicates a Potential Role for
Faisal Alhosani1,2,3,4, Burcu Yener Ilce1, Reem Sami Alhamidi1
1Research Institute of Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates.
International Journal of Molecular Sciences
|October 16, 2024
Summary
CARD11 overexpression worsens colorectal cancer (CRC) prognosis by promoting cell growth, tissue remodeling, and immune response. It also enhances CRC invasiveness through pathways like chemotaxis and extracellular matrix organization.
Area of Science:
- Molecular Biology
- Oncology
- Immunology
Background:
- The nuclear factor-κB (NF-κB) pathway is crucial for inflammation and immunity, with its dysregulation linked to diseases like cancer.
- CARD11 is a key signaling molecule in the BCL10-MALT1 complex, downstream of the NF-κB pathway.
- Understanding CARD11's role is vital for elucidating colorectal cancer (CRC) progression.
Purpose of the Study:
- To investigate how CARD11 overexpression exacerbates colorectal cancer (CRC) prognosis.
- To identify cellular pathways influenced by CARD11 in CRC.
- To analyze the correlation between CARD11 expression levels and CRC progression in cell lines and patient samples.
Main Methods:
- Transcriptomic analysis of CARD11-overexpressed CRC cell lines (HCT-116, HT-29) versus control cell lines.
- Comparative transcriptomic analysis of CRC patient samples (adenoma and carcinoma) with varying CARD11 expression levels (low vs. high).
- Bioinformatics analysis, including absolute Gene Set Enrichment Analysis (absGSEA), to identify key genes and pathways.
Main Results:
- CARD11 overexpression in cell lines promoted cell growth, tissue remodeling, and immune response, alongside pathways involved in chemotaxis and extracellular matrix organization, indicating increased CRC invasiveness.
- Key co-expressed genes like EP300, KDM5A, HIF1A, NFKBIZ, and DUSP1 mediate CARD11's effects on growth and remodeling.
- In patient samples, high CARD11 expression correlated with increased immune microenvironment genes in adenomas and significant upregulation of cancer-related genes (MAPK8IP2, EMB, EPHB6, CPEB4) in carcinomas.
Conclusions:
- CARD11 plays a significant role in colorectal cancer progression, influencing cell growth, tissue remodeling, immune response, and invasiveness.
- Specific genes and pathways activated by CARD11 overexpression contribute to the transition to a more aggressive cancer stage.
- CARD11 expression levels are a potential prognostic marker for colorectal cancer.
