Role of MMP۷ in Colorectal Cancer: Expression, Pathway Interactions, and SNP Impact

Colorectal cancer is one of the leading causes of cancer-related deaths worldwide. Matrix metalloproteinases (MMPs), particularly MMP۷, are crucial in tumorigenesis, especially in cancer invasion and metastasis, by degrading extracellular matrix components. According to the Reactome pathway database (R-HSA-۱۵۹۲۳۸۹), MMP۷ interacts with other MMP family members, including MMP۱, MMP۳, and MMP۱۰. In the KEGG pathway, MMP۷ is also involved in the Wnt signaling pathway, interacting with key genes like AXIN۲ and NKD۱, which are linked to cancer progression. Recent findings suggest that hsa-miR-۱۲۲-۵p can regulate MMP۷ expression, and it also interacts with the long non-coding RNA (lncRNA) C۹orf۱۴۷, which may modulate MMP۷ in colorectal cancer. This study investigates MMP۷ expression, its interactions, and the impact of a specific SNP using bioinformatics tools. Method: Microarray data from GEO, specifically dataset GSE۸۶۷۱, were used to compare gene expression in cancerous and healthy colorectal tissues. The target gene was MMP۷. Pathway analyses were conducted using Reactome and KEGG databases to identify MMP۷’s involvement in relevant pathways and its gene interactions. STRING database was utilized to explore MMP۷’s protein-protein interaction network, focusing on its interaction with CD۴۴, a protein involved in cancer cell adhesion. Additionally, the SNP rs۱۳۹۵۹۷۶۸۳, which leads to an asparagine-to-lysine substitution, was analyzed for its effect on protein function and interactions. miRBase and miRTarBase were used to confirm interactions between hsa-miR-۱۲۲-۵p, MMP۷, and C۹orf۱۴۷. Results: Microarray analysis indicated a significant upregulation of MMP۷ in colorectal cancer tissues compared to healthy controls. Pathway enrichment confirmed MMP۷’s involvement in the Activation of Matrix Metalloproteinases pathway, where it interacts with MMP۱, MMP۳, and MMP۱۰. Further analysis of the Wnt signaling pathway in KEGG revealed that MMP۷ interacts with AXIN۲ and NKD۱, both crucial regulators of this pathway. The SNP rs۱۳۹۵۹۷۶۸۳ alters the amino acid sequence of MMP۷, potentially affecting its interaction with CD۴۴, leading to enhanced cell adhesion and migration in colorectal cancer. STRING analysis highlighted a strong interaction between MMP۷ and CD۴۴, supported by ۱۰ interaction nodes. Additionally, hsa-miR-۱۲۲-۵p was identified as a microRNA with a predicted binding site in the ۳' UTR of MMP۷. Its downregulation, alongside its interaction with C۹orf۱۴۷, may contribute to MMP۷ overexpression in colorectal cancer tissues. Conclusion: The overexpression of MMP۷ in colorectal cancer, its involvement in matrix metalloproteinase activation, and Wnt signaling pathways underscore its critical role in cancer progression. The SNP rs۱۳۹۵۹۷۶۸۳ highlights MMP۷’s potential to influence protein interactions, particularly with CD۴۴, which may enhance cancer cell adhesion and invasion. The regulatory role of hsa-miR-۱۲۲-۵p, in conjunction with the lncRNA C۹orf۱۴۷, suggests that the downregulation of these molecules may lead to the overexpression of MMP۷, further promoting tumor growth. These findings underscore the potential of MMP۷, along with its regulatory microRNA and lncRNA, as biomarkers and therapeutic targets for colorectal cancer.

کلیدواژه ها:

colorectal cancer ، bioinformatics ، microarray ، biomarker