Key target genes of miR-625-5p in colorectal cancer: uncovering novel therapeutic targets within regulatory network.

BACKGROUND

Colorectal cancer (CRC) is usually diagnosed when therapeutic options are limited, highlighting the need for novel molecular targeted therapies. MicroRNAs, as important regulators in cancer-related pathways, may provide therapeutic targets through their gene networks; however, the role of the miR-625-5p network in CRC remains unclear. Therefore, this study aimed to identify potential therapeutic targets in CRC through miR-625-5p-regulated network analysis.

METHODS

miR-625 expression in TCGA samples was analyzed to assess its potential role in CRC development/progression. miR-625-5p targets were integrated from multiple resources to construct a protein-protein interaction network (PPIN) and identify clusters and key hub genes using Cytoscape. Key hub genes underwent enrichment analysis using DAVID and CancerHallmarks, followed by validation in independent CRC datasets from GEO and TCGA. Validated Key hub genes were further analyzed using TNMplot and Kaplan-Meier survival analysis to assess their expression patterns and prognostic significance, respectively. Druggability of the prognostic final hub gene was assessed using the Open Targets Platform.

RESULTS

miR-625 was significantly downregulated in CRC, particularly in advanced stages (p-value < 0.05). PPIN analysis of 755 target genes identified 24 key hub genes and four functional clusters. Enrichment analysis of key hub genes showed involvement in regulation of apoptotic processes, programmed cell death, and cancer-related pathways. Five candidate genes were validated in GEO and TCGA datasets; three were confirmed in TNMplot, and only HSP90AB1 was associated with poorer disease-free survival (p-value < 0.05) and exhibited druggable potential in CRC.

CONCLUSION

HSP90AB1 is a candidate therapeutic target in CRC.