Abstract: Objective To observe the regulation of miR-504 in mouse models and the biological behavior of breast cancer cells, find the key target genes of miR-504 in the regulation process, and explore the working mechanism of miR-504 in breast cancer. Methods A mouse model of breast cancer was established and the effect of miR-504 on tumor growth was observed. Target genes of miR-504 were screened by Target Scaning and confirmed by double luciferase reporter gene assay. RT-qPCR and Western blot were used to detect proteasome activator complex subunit 3(PSME3) expression in breast cancer and adjacent tissues. The effects of miR-504 and PSME3 on proliferation, cycle and migration of human breast cancer cell line MCF-7 were determined by CCK8 assay, flow cytometry and Transwell assay. Results It was found that miR-504 inhibited tumor growth in nude mouse xenograft model of breast cancer(P<0.01). PSME3 was a target gene of miR-504, and its expression in breast cancer tissues was significantly increased. Up-regulation of miR-504 expression could inhibit the expression of PSME3 (P<0.01). Compared with NC group, miR-504 mimic group could inhibit the proliferation, S-phase arrest and migration ability of breast cancer cells, while compared with miR-504 mimic group, miR-504 mimic+PSME3 group, increased proliferation the proportion of S-phase and migration ability(P<0.01)in MCF-7 cell. Conclusions miR-504 may play an anti-cancer role in breast cancer by targeting PSME3 regulation.

Key words: breast cancer, miR-504, proteasome activator complex subunit 3, MCF-7 cell, proliferation