MicroRNA-224 and its target CAMKK2 synergistically influence tumor progression and patient prognosis in prostate cancer
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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.
KeywordsProstate cancer MicroRNA-224 Calcium/calmodulin-dependent protein kinase kinase 2 Clinicopathological characteristic Overall survival
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.
Conflicts of interest