期刊
TUMOR BIOLOGY
卷 36, 期 8, 页码 5987-5997出版社
SAGE PUBLICATIONS LTD
DOI: 10.1007/s13277-015-3275-8
关键词
miR-124; CDK4; Breast cancer; Proliferation; Cell cycle
类别
资金
- National Natural Science Foundation of China [81272323]
- Natural Science Foundation of Jiangsu Province [BK2012590]
- Technology Project of Changzhou Social Development [CE20125019, CE20125024, CE20135044]
- key project of the Changzhou Health Bureau [ZD201201, ZD201307]
Studies have shown that microRNAs (miRNAs) are involved in the malignant progression of human cancer. However, little is known about the potential role of miRNAs in breast carcinogenesis. miR-124 expression in breast cancer tissue was measured by quantitative real-time PCR (qRT-PCR). Target prediction algorithms and luciferase reporter gene assays were used to investigate the target of miR-124. Breast cancer cells growth was regulated by overexpression or knockdown miR-124. At the end of the study, tumor-bearing mice were tested to confirm the function of miR-124 in breast cancer. In this study, we demonstrated that the expression of miR-124 was significantly downregulated in breast cancer tissues compared with matched adjacent non-neoplastic tissues. We identified and confirmed that cyclin-dependent kinase 4 (CDK4) was a direct target of miR-124. Overexpression of miR-124 suppressed CDK4 protein expression and attenuated cell viability, proliferation, and cell cycle progression in MCF-7 and MDA-MB-435S breast cancer cells in vitro. Overexpression of CDK4 partially rescued the inhibitory effect of miR-124 in the breast cancer cells. Moreover, we found that miR-124 overexpression effectively repressed tumor growth in xenograft animal experiments. Our results demonstrate that miR-124 functions as a growth-suppressive miRNA and plays an important role in inhibiting tumorigenesis by targeting CDK4.
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