Identification of novel exosomal miRNAs and their role in diagnosis and prognosis of Triple Negative Breast Cancer

Exosomal miRNAs have been identified as key secretory biomarkers facilitating intercellular communication in the tumor microenvironment, with substantial potential as diagnostic, prognostic, and therapeutic targets. Our research focuses on the role of exosomal miRNAs in triple-negative breast cancer (TNBC) and cancer stem cells, contributing to tumor progression and relapse. Through meta-analysis and data mining, we identified five differentially expressed miRNAs- hsa-miR-6803, hsa-miR-1180, hsa-miR-4728, hsa-miR-1915 and hsa-miR-940 in breast cancer. Target predictions, GO and KEGG enrichment analyses have indicated the potential role of these oncomiRs in Wnt, Notch and EGFR signalling pathways involved in tumor progression. While the panel of five miRNAs was found to be over-expressed in breast cancers, they have not been reported in TNBC and TNBCSCs, making them ideal biomarkers for TNBC. These oncomiRs were consistently detected across TNBC cell lines, TNBCSCs and further validated in TNBC tumor tissues (n = 15). Interestingly, a highly significant overexpression of two of the five specific miRNAs- hsa-miR-1180 and hsa-miR-4728 and their high tumorigenic validation in an invasion, migration and siRNA analysis indicates their potential as prognostic and therapeutic target(s). The presence of these miRNAs in TNBC cell lines, TNBCSCs and circulatory exosomes and their elevated expression in tumor tissue highlights their significance as potential biomarkers for TNBC. We suggest that these five specific secretory miRNAs could function as a liquid biopsy tool, not only for the diagnosis of tumor progression but may also provide a reference value for early detection as well as for monitoring the prognosis of TNBCs