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Oncol Lett. 2017 Sep;14(3):3455-3462. doi: 10.3892/ol.2017.6651. Epub 2017 Jul 21.

Hsa-miR-599 suppresses the migration and invasion by targeting BRD4 in breast cancer.

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Department of Breast Surgery, Weifang People's Hospital, Weifang, Shandong 261042, P.R. China.
Emergency Department of Weifang Traditional Chinese Hospital, Weifang, Shandong 261042, P.R. China.
Radiotherapy Department, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261042, P.R. China.


Breast cancer is the second leading cause of cancer-associated mortality in females in the USA. Hsa-miR-599 was demonstrated to function as a tumour suppressor during cancer progression. However, the function and mechanism of the hsa-miR-599 in human breast cancer remain elusive. Thus, the aim of the present study was to investigate the potential role of hsa-miR-599 in breast cancer biology. The expression levels of hsa-miR-599 in 40 pairs of surgical specimens and human breast cancer cell lines were detected using quantitative polymerase chain reaction analysis. The overexpression of hsa-miR-599 was established by transfecting mimics into the MCF-7 and MDA-MB-231 cell lines. Cell counting kit-8, colony formation and transwell assays were used to investigate the potential function of hsa-miR-599 in MCF-7 and MDA-MB-231 cell lines. Luciferase assays combined with western blot analysis was performed to validate the regulation of a putative target of hsa-miR-599. The results demonstrated that hsa-miR-599 was downregulated in the breast cancer tissues and breast cancer cell lines. Overexpression of hsa-miR-599 was revealed to inhibit the viability and proliferation of cell in vitro and tumour growth in vivo. The results of the luciferase assay indicate that bromodomain containing 4 (BRD4) is a direct target of hsa-miR-599. Furthermore, the xenograft mouse model demonstrated that overexpressed hsa-miR-599 reduced BRD4 expression. These results suggest that hsa-miR-599 serves as an oncosuppressive microRNA that impairs breast cancer tumorigenesis and progression by directly targeting BRD4. Furthermore, increased BRD4 expression partially reversed the suppressive effect of hsa-miR-599. In conclusion, the results of the present study demonstrated that hsa-miR-599 suppressed breast cancer progression by downregulating BRD4. The overexpression of hsa-miR-599 may be considered as a novel therapeutic target for the treatment of patients with breast cancer.


BRD4; breast cancer; hsa-miR-599; migration and invasion; proliferation

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