miR-124 inhibits cell proliferation in breast cancer through downregulation of CDK4

被引:60
|
作者
Feng, Tongbao [1 ,2 ]
Xu, Dongqin [1 ]
Tu, Chao [1 ]
Li, Wenjing [1 ]
Ning, Yongling [1 ,2 ]
Ding, Jun [1 ,2 ]
Wang, Shizhong [1 ,2 ]
Yuan, Liudi [3 ]
Xu, Ning [4 ]
Qian, Keqing [1 ]
Wang, Yong [2 ]
Qi, Chunjian [1 ]
机构
[1] Nanjing Med Univ, Affiliated Hosp, Inst Oncol, Changzhou Peoples Hosp 2, Changzhou 213003, Peoples R China
[2] Nanjing Med Univ, Affiliated Hosp, Dept Gen Surg, Changzhou Peoples Hosp 2, Changzhou 213003, Peoples R China
[3] Southeast Univ, Inst Life Sci, State Educ Minist Key Lab Dev Genes & Human Dis, Nanjing 210096, Jiangsu, Peoples R China
[4] Lund Univ, Sect Clin Chem & Pharmacol, Dept Lab Med, S-22185 Lund, Sweden
基金
中国国家自然科学基金;
关键词
miR-124; CDK4; Breast cancer; Proliferation; Cell cycle; HEPATOCELLULAR-CARCINOMA; TUMOR INVASION; TARGETING CDK4; GLIOMA-CELLS; MICRORNA; METASTASIS; SENESCENCE; AMPLIFICATION; GROWTH; TUMORIGENESIS;
D O I
10.1007/s13277-015-3275-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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.
引用
收藏
页码:5987 / 5997
页数:11
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