MicroRNA-224 and its target CAMKK2 synergistically influence tumor progression and patient prognosis in prostate cancer.
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.
Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou, 510515, China.
Hao
H
Fu
Hui-chan
HC
He
Zhao-dong
ZD
Han
Yue-ping
YP
Wan
Hong-wei
HW
Luo
Ya-qiang
YQ
Huang
Chao
C
Cai
Yu-xiang
YX
Liang
Qi-shan
QS
Dai
Fu-neng
FN
Jiang
Wei-de
WD
Zhong
D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase / Q000235:genetics* / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics
D014408:Biomarkers, Tumor; C546140:MIRN224 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; C517698:CAMKK2 protein, human; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase