MiR-651-3p/CAV1/EGFR axis Modulates Progression and Vasculogenic Mimicry in Triple-negative Breast Cancer

Abstract

Background: Breast cancer (BC) has become the most common type of cancer and the second most common cause of cancer-related death. In comparison with other subtypes of breast cancer, triple-negative breast cancer (TNBC) is highly aggressive, more likely to metastasize, and has a shorter survival time. MiRNAs play an inhibitory or promoting role in cancer, and are involved in several cell signaling pathways, including growth, proliferation, differentiation, and survival. Vasculogenic mimicry (VM) is associated with invasive disease, tumor spread, metastasis, and poor prognosis. Additional research is needed to determine the mechanisms governing VM formation in TNBC. Methods: We measured RNA and protein expression using quantitative real-time PCR (RT-qPCR) and western blotting. Assays assessing cell proliferation were conducted with CCK-8, cell cycle, and colony formation. Cell migration and invasion were evaluated using transwells, scratch tests, and high-intensity imaging. Luciferase reporter assays were used to confirm miR-651-3p and CAV1 target relationships. Results: In TNBC, miR-651-3p was significantly overexpressed, implicating it as an oncogene. By inhibiting CAV1 transcriptional synthesis, miR-651-3p can enhance the activity of EGFR pathways, leading to promotion of TNBC proliferation, VM formation, and migration. Conclusion: It was determined that miR-651-3p/CAV1/EGFR axis could be a therapeutic target for TNBC in this study.