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

  • Research Article
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Tumor Biology

Abstract

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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Acknowledgments

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

None

Author contributions

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.

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Authors and Affiliations

  1. Oncology Institute, The Affiliated Hospital of Nanjing Medical University, Changzhou No.2 People’s Hospital, Changzhou, 213003, China

    Tongbao Feng, Dongqin Xu, Chao Tu, Wenjing Li, Yongling Ning, Jun Ding, Shizhong Wang, Keqing Qian & Chunjian Qi

  2. Department of General Surgery, The Affiliated Hospital of Nanjing Medical University, Changzhou No.2 People’s Hospital, Changzhou, 213003, China

    Tongbao Feng, Yongling Ning, Jun Ding, Shizhong Wang & Yong Wang

  3. State Education Ministry’s Key Laboratory of Developmental Genes and Human Diseases, Institute of Life Sciences, Southeast University, Nanjing, 210096, China

    Liudi Yuan

  4. Section of Clinical Chemistry & Pharmacology, Department of Laboratory Medicine, Lund University, 221 85, Lund, Sweden

    Ning Xu

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  1. Tongbao Feng
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Correspondence to Chunjian Qi.

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Feng, T., Xu, D., Tu, C. et al. miR-124 inhibits cell proliferation in breast cancer through downregulation of CDK4. Tumor Biol. 36, 5987–5997 (2015). https://doi.org/10.1007/s13277-015-3275-8

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  • DOI: https://doi.org/10.1007/s13277-015-3275-8

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