miR-124 inhibits cell proliferation in breast cancer through downregulation of CDK4
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.
KeywordsmiR-124 CDK4 Breast cancer Proliferation Cell cycle
This work was supported by grants from the National Natural Science Foundation of China (81272323), the Natural Science Foundation of Jiangsu Province (BK2012590), the Technology Project of Changzhou Social Development (CE20125019, CE20125024, CE20135044), and the key project of the Changzhou Health Bureau (ZD201201, ZD201307).
Conflicts of interest
T.B. and C.Q. provided the original idea and were responsible for the study design, analysis and interpretation of data, statistical analyses, and writing of the manuscript; T.B., D.X., L.Y., N.X., K.Q., and Y.W. were responsible for the analysis and interpretation of data and statistical analysis; C.T., W.L., Y.N., and J.D. were responsible for technical, material support and statistical analyses; S.W. was responsible for data collection and technical supports; All authors read and approved the final manuscript.
- 1.Desantis C, Ma J, Bryan L, Jemal A: Breast cancer statistics, 2013. CA Cancer J Clin 2013.Google Scholar
- 3.van den Hurk CJ, Eckel R, van de Poll-Franse LV, Coebergh JW, Nortier JW, Holzel D, et al. Unfavourable pattern of metastases in m0 breast cancer patients during 1978-2008: a population-based analysis of the Munich Cancer Registry. Breast Cancer Res Treat. 2011;128:795–805.CrossRefPubMedGoogle Scholar
- 41.Huang Z, Choi BK, Mujoo K, Fan X, Fa M, Mukherjee S, Owiti N, Zhang N, An Z: The e3 ubiquitin ligase nedd4 negatively regulates her3/erbb3 level and signaling. Oncogene 2014.Google Scholar