Unveiling the MiR-GSK3B-Target Gene Axis in Colorectal Cancer: An in Silico Exploration

Fatemeh Hassanzadeh Naeimi; Iman Salahshourfar; Marveh Rahmati; Reza Shirkoohi

doi:10.31557/APJCB.2026.11.3.835

Authors

Fatemeh Hassanzadeh Naeimi Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Iman Salahshourfar Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Marveh Rahmati Cancer Biology Research Center, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.
Reza Shirkoohi Cancer Biology Research Center, Cancer Institute, Imam Khomeini Hospital Complex, Tehran University of Medical Sciences, Tehran, Iran.

DOI:

https://doi.org/10.31557/APJCB.2026.11.3.835

Keywords:

Colorectal cancer, GSK3B signaling pathway, miRNAs, miR-16-5p, miR-214-5p, miR-19-3p, MACF1, BRD7, GSKIP, FSBP, in silico analysis, pathway analysis, protein-protein interaction, TCGA, prognosis.

Abstract

Background: Colorectal cancer (CRC) remains a significant public health burden, prompting exploration of novel therapeutic targets. The Wnt signaling pathway plays a crucial role in CRC pathogenesis, regulating critical processes like proliferation, migration, and cell fate. MicroRNAs (miRNAs), potent regulators of gene expression, hold immense potential for cancer therapy. This in silico study delves into the regulatory interplay between three miRNAs, miR-16-5p, miR-214-5p, and miR-19-3p, and their downstream targets within the Wnt signaling pathway in SW480 colorectal cancer cells.

Materials and Methods: A comprehensive bioinformatics approach was employed. Target prediction databases and miRNA-gene expression datasets were utilized to identify potential interactions between the miRNAs and key Wnt pathway genes, including β-catenin, cyclin D1, and TCF/LEF transcription factors. Functional enrichment analysis and protein-protein interaction (PPI) network construction assessed the relevance of these targets. Additionally, The Cancer Genome Atlas (TCGA) data revealed miRNA expression profiles and survival outcomes to analyze clinical significance.

Results: In silico predictions identified putative binding sites for all three miRNAs within the 3’ untranslated regions (UTRs) of Wnt pathway genes. Functional enrichment analysis confirmed these target genes’ involvement in crucial cancer-related pathways, including cell cycle regulation, Wnt signaling, and epithelial-to-mesenchymal transition (EMT). PPI network analysis further supported their interconnected roles in these processes. Notably, TCGA data revealed downregulation of miR-16-5p, miR-214-5p, and miR-19-3p in CRC tissues compared to normal controls, with low miRNA expression correlating with poor patient prognosis.

Conclusion: This in silico investigation provides compelling evidence for a regulatory loop involving miR-16-5p, miR-214-5p, and miR-19-3p targeting key Wnt pathway genes in SW480 colorectal cancer cells. Downregulation of these miRNAs potentially contributes to CRC progression, highlighting their potential as therapeutic targets or prognostic biomarkers.