hsa-miR-9-FABP7 axis as a predictive biomarker for metastatic progression in triple-negative breast cancer: An...

Metastasis remains the primary cause of breast cancer mortality. Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype. It lacks targeted therapies and carries a high risk of metastasis. MiRNAs are one of the potential diagnostics and therapeutic biomarkers, given that the regulation of mRNA is critical for tumor growth and metastatic transformation of tumor cells. Identifying the differential expression of the miRNA-mRNA axis at the primary tumor site will provide novel molecular mechanisms for metastasis initiation. In this study, we applied an integrated approach to explore the metastasis-specific miRNA-mRNA regulatory axis in TNBC using TCGA-derived miRNA-seq and RNA-seq data. Differential expression analysis between metastatic and non-metastatic TNBC patient data identified 11 dysregulated miRNAs, of which 8 showed linear expression changes with increasing disease aggressiveness. Among them, hsa-miR-1-1/2, hsa-miR-9, and hsa-miR-1180 displayed strong diagnostic potential (AUC >0.8) and significant associations with overall survival in metastatic TNBC patients. Parallel RNA-seq analysis revealed 36 differentially expressed genes (DEGs). Target prediction highlighted that only hsa-miR-9-5p targeted three of the 36 DEGs-FABP7, GPR26, and UNC5D, where FABP7 demonstrated strong association with cancer pathways. The expression of these genes was also correlated with the overall survival of the TNBC patients. Validation of this axis in various breast cancer cells (metastatic and non-metastatic) was performed, and the results indicated an inverse expression pattern of hsa-miR-9-5p and FABP7, especially in metastatic TNBC cells. These findings propose the hsa-miR-9-FABP7 axis as a promising biomarker signature for predicting metastatic potential from primary TNBC tumors.