Abstract
Objective To investigate the role and mechanism of miR-6767-5p in breast cancer (BC). Methods: We explored the effects of miR-6767-5p on the proliferation, migration, and invasion of BC cells in vitro and in vivo through CCK-8, EdU, Transwell, and subcutaneous tumorigenesis experiments in nude mice and a tail vein lung metastasis model. Cysteine-rich intestinal protein 2 (CRIP2) was validated as a target gene of miR-6767-5p through dual-luciferase reporter assays, quantitative polymerase chain reaction (qPCR), and western blot (WB) analysis. WB was conducted to investigate the impact of miR-6767-5p on the NF-κB signaling pathway and its association with the epithelial‒mesenchymal transition (EMT). Coimmunoprecipitation, chromatin immunoprecipitation, qPCR and WB were used to verify the possible relationships among SP1, c-jun and miR-6767-5p. The relationships between miR-6767-5p and the stage and prognosis of breast cancer were investigated by in situ hybridization. Results: (1) Knockdown of miR-6767-5p inhibits the proliferation, migration, and invasion of BC cell in vivo and in vitro. (2) miR-6767-5p targets CRIP2. (3) miR-6767-5p activates NF-κB and the EMT by inhibiting CRIP2. (4) miR-6767-5p can be upregulated by SP1. (5) Mitogen-activated protein kinase kinase 4 (MAP2K4) induces miR-6767-5p expression through the PI3K/AKT/c-jun/SP1 axis. (6) High expression of miR-6767-5p is associated with a poor prognosis for patients with breast cancer. Conclusions: (1) miR-6767-5p is highly expressed in BC cells, stimulating their proliferation, migration, and invasion both in vivo and in vitro. (2) miR-6767-5p activates the NF-κB signaling pathway and the EMT by specifically inhibiting CRIP2. (3) The expression of miR-6767-5p is regulated by MAP2K4 through the upregulation of c-jun. (4) The expression of miR-6767-5p is positively correlated with the stage of breast cancer and a poor prognosis for patients.