hsa-miR-۳۷۰-۳p regulates the Phospholipase C-mediated Cascade pathway in the Colorectal cancer development by modifying the expression of FGFR۳: Integrated High-throughput bioinformatics investigation

Colorectal cancer (CRC) is a multifactorial disease and ranks as the third most frequently diagnosed cancer and the second leading cause of cancer-related mortality globally. Among males, colorectal canser is the third most commonly diagnosed cancer, while among females, it ranks second. The epithelial cells of the colorectal mucosa can undergo various stages of hyperplasia, including mild, moderate, and severe atypical hyperplasia, as well as the formation of adenomas. These conditions have the potential to progress into carcinoma. This progression is typically triggered by carcinogenic factors that induce structural alterations in DNA, ultimately leading to the malignant transformation of cells into cancer. In this study, we performed an integrated bioinformatics and systems biology investigation to evaluate a novel regulatory network in colorectal cancer. Methods: Based on microarray analysis, dysregulated protein-coding genes were detected in colorectal cancer patients (GSE۲۶۵۹۰۷). Pathway enrichment analysis was performed using the REACTOME online database. Protein-protein correlation analysis was performed using the STRING online database. Microarray analysis was performed on the dataset using GEO۲R, ENCORI, and Enrichr for pathway enrichment and gene ontology analyses. Results: Based on microarray analysis, ACAP۳, FGFR۳, and CNTFR have a significantly low expression in colorectal cancer patients compared to the control (logFC < ۰, adj. P. Value < ۰.۰۰۰۰۰۱). Based on pathway enrichment analysis, ACAP۳ regulates the Estrogen signaling pathway and FGFR۳ regulates the Phospholipase C-mediated Cascade pathway. Protein-protein interaction analysis revealed that FGFR۳ has significant interaction with FGF۲, FGF۸ and FGF۹ proteins. miRNA interaction analysis revealed the top ۵ regulatory miRNAs interacted with FGFR۳. hsa-miR-۳۷۰-۳p has a stronger and the most significant interaction with FGFR۳ mRNA (score: ۱, position: ۳′UTR, binding energy: -۲۹.۵). Conclusion: hsa-miR-۳۷۰-۳p could regulate the Phospholipase C-mediated Cascade pathway in colorectal cancer patients, by decreasing the expression level of FGFR۳ as a potential tumor-suppressor and diagnostic biomarker of colorectal cancer.

کلیدواژه ها:

colorectal cancer ، microRNA interaction ، Systems Biology ، Microarray analysis ، Pathway enrichment