Effect of Exosome-loaded hsa-miR-203a-3p on Triple Negative Breast Cancer Cell Viability, Migration, and Gene Targets: In Silico and In Vitro Study

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype lacking targeted therapy options. MicroRNA-based therapy, particularly hsa-miR-203a-3p, has shown tumor-suppressive potential; however, an effective delivery system is required to enhance its stability and cellular uptake. Exosomes represent a promising natural carrier for miRNA delivery.

Exosomes derived from UC-MSCS secretome were isolated and characterized using Nanoparticle Tracking Analysis (NTA). Exosome-loaded hsa-miR-203a-3p (ExomiR) was generated using the Exo-Fect transfection system. Functional assays, including MTT and wound-healing assays, were performed on TNBC Hs578T cells. qRT-PCR was used to measure miRNA uptake. In silico analysis utilizing TargetScan, TarBase, DAVID, and the TNBC dataset GSE65194 was performed to identify target genes and pathways.

ExomiR significantly reduced TNBC cell viability in a dose-dependent manner, with viability dropping below 50% at the 2×dose. Migration assays showed the strongest inhibition at 1×dose at 12 hours (37.4±13%, P <0.01) and at 2×dose at 24 hours (32.3±6.18%, P <0.0001). ExomiR treatment yielded an 87-fold increase in intracellular hsa-miR-203a-3p expression. In silico analysis identified 23 upregulated TNBC-related target genes, including CCNB1 and CDK1, which regulate cell cycle, p53 signaling, and cellular senescence pathways.

Exosome-mediated delivery enhances hsa-miR-203a-3p uptake and effectively suppresses cell viability and migration in TNBC cells. Computational analysis further indicates that hsa-miR-203a-3p regulates key oncogenic pathways, supporting its potential as a therapeutic agent.

Abstract from PubMed Central (PMID 43005272, PMC13745380). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.