MicroRNA-224 and its target CAMKK2 synergistically influence tumor progression and patient prognosis in prostate cancer
MicroRNA-224 and its target CAMKK2 synergistically influence tumor progression and patient prognosis in prostate cancer
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MicroRNA-224 及其靶标 CAMKK2 协同影响前列腺癌的肿瘤进展和患者预后
DOI：
10.1007/s13277-014-2805-0
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发表时间：
2015-03-01
期刊：
影响因子：
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通讯作者：
Zhong, Wei-de
中科院分区：
文献类型：
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作者：
Fu, Hao;He, Hui-chan;Zhong, Wei-de
我们先前证明，microRNA（miR）-224在人前列腺癌（PCa）组织中的表达显著降低，并预测患者的预后不良。然而，miR-224的潜在机制尚未完全阐明。在这项研究中，钙/钙调蛋白依赖性蛋白激酶激酶2（CAMKK 2）被确定为miR-224的靶基因。在体外实验中，我们发现miR-224的高表达可以通过调节CAMKK 2的表达来抑制PCa细胞的增殖和细胞周期。此外，PCa组织中miR-224与CAMKK 2 mRNA的表达水平呈显著负相关（斯皮尔曼相关性：r=-0.66，P = 0.004）。miR-224低表达和CAMKK 2高表达（miR-224-low/CAMKK 2-high）与晚期临床分期密切相关（P= 0.028）。此外，miR-224-低/CAMKK 2-高表达的PCa患者的总生存期比两种分子的其他表达模式的患者更短。总之，我们的数据提供了令人信服的证据，证明miR-224及其靶基因CAMKK 2可能协同促进PCa的恶性进展。联合检测miR-224和CAMKK 2表达可有效预测PCa患者的预后，并可能成为一种新的标志物，可提供额外的预后信息。
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.