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MicroRNA-224 and its target CAMKK2 synergistically influence tumor progression and patient prognosis in prostate cancer

  • Research Article
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Tumor Biology

Abstract

We previously demonstrated that microRNA (miR)-224 expression was significantly reduced in human prostate cancer (PCa) tissues and predicted unfavorable prognosis in patients. However, the underlying mechanisms of miR-224 have not been fully elucidated. In this study, calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) was identified as a target gene of miR-224. Then, we found that enforced expression of miR-224 could suppress PCa cell proliferation and cell cycle by regulating the expression of CAMKK2 in vitro. In addition, the expression levels of miR-224 in PCa tissues were negatively correlated with those of CAMKK2 mRNA significantly (Spearman’s correlation: r = −0.66, P = 0.004). Moreover, combined low miR-224 expression and high CAMKK2 expression (miR-224-low/CAMKK2-high) was closely correlated with advanced clinical stage (P = 0.028). Furthermore, PCa patients with miR-224-low/CAMKK2-high expression more frequently had shorter overall survival than those in groups with other expression patterns of two molecules. In conclusion, our data offer the convincing evidence that miR-224 and its target gene CAMKK2 may synergistically contribute to the malignant progression of PCa. Combined detection of miR-224 and CAMKK2 expressions represents an efficient predictor of patient prognosis and may be a novel marker which can provide additional prognostic information in PCa.

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Acknowledgments

This work was supported by grants from National Natural Science Foundation of China (81170699, 81272813, 81200550), Science and Technology Project of Guangdong Province (2012B031800008), Guangzhou Municipal Science and Technology Key Project (11C23150711), Projects of Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics.

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Authors and Affiliations

  1. Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou, 510515, China

    Hao FU, Hong-wei Luo, Ya-qiang Huang, Chao Cai & Wei-de Zhong

  2. Department of Urology, Affiliated Nanhua Hospital, University of South China, Hengyang, 421002, China

    Hao FU

  3. Department of Urology, Huadu District People’s Hospital, Southern Medical University, Guangzhou, People’s Republic of China

    Yue-ping Wan & Wei-de Zhong

  4. Department of Urology, Guangdong Key Laboratory of Clinical Molecular Medicine and Diagnostics, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, 510180, China

    Hui-chan He, Zhao-dong Han, Yu-xiang Liang, Qi-shan Dai, Fu-neng Jiang & Wei-de Zhong

  5. Department of Urology, Guangzhou First People’s Hospital, Guangzhou Medical University, Guangzhou, 510180, China

    Wei-de Zhong

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  1. Hao FU
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Correspondence to Wei-de Zhong.

Additional information

Hao FU, Hui-chan He, and Zhao-dong Han contributed equally to this article.

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Supplement Fig. 1

Original data of transwell and wound-healing assay. Overexpression of miR-224 fail to promote invasion and migration in CAMKK2 knockdown DU145 cells. (GIF 660 kb)

High resolution (TIFF 13041 kb)

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FU, H., He, Hc., Han, Zd. et al. MicroRNA-224 and its target CAMKK2 synergistically influence tumor progression and patient prognosis in prostate cancer. Tumor Biol. 36, 1983–1991 (2015). https://doi.org/10.1007/s13277-014-2805-0

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  • DOI: https://doi.org/10.1007/s13277-014-2805-0

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