Exosomal miR-155-5p Modulates Breast Cancer Proliferation and Metastasis Via NF-κB Activation

Breast cancer (BC) represents a major contributor to cancer-associated deaths among women, underscoring the need for novel therapeutic approaches. This study explores the role of miR-155-5p as an oncogenic driver in BC progression through a multi-omics approach. Elevated miR-155-5p expression was observed in serum exosomes and tumor tissues, with its upregulation correlating with advanced pathological stages, lymph node metastasis, and unfavorable clinical outcomes. Functional experiments demonstrated that miR-155-5p enhances cellular proliferation, motility, and invasive capacity while inhibiting apoptosis in BC. Mechanistically, miR-155-5p exerts its effects by directly suppressing Nedd4 Family Interacting Protein 1 (NDFIP1), thereby initiating activation of the NF-κB axis. This activation was characterized by increased nuclear translocation of NF-κB p65 and enhanced secretion of inflammatory cytokines, including IL-6 and TNF-α. In vivo, knockdown of miR-155-5p effectively suppressed tumor growth and metastasis, with these effects reversed by silencing NDFIP1. These results highlight the miR-155-5p/NDFIP1/NF-κB axis as a critical pathway in BC progression, providing new insights into its molecular mechanisms. miR-155-5p emerges as a promising diagnostic marker and therapeutic candidate, suggesting the feasibility of miRNA-based interventions in BC treatment. This study highlights the pivotal role of integrative omics technologies in uncovering cancer-related regulatory networks.