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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.

Author information

1
Department of Breast Surgery, Weifang People's Hospital, Weifang, Shandong 261042, P.R. China.
2
Emergency Department of Weifang Traditional Chinese Hospital, Weifang, Shandong 261042, P.R. China.
3
Radiotherapy Department, Affiliated Hospital of Weifang Medical University, Weifang, Shandong 261042, P.R. China.

Abstract

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.

KEYWORDS:

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

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