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miR-199a-3p Inhibits Aurora Kinase A and Attenuates Prostate Cancer Growth
- Source :
- American Journal of Pathology; May 2014, Vol. 184 Issue: 5 p1541-1549, 9p
- Publication Year :
- 2014
-
Abstract
- Prostate cancer (PCa) is the most common solid tumor malignancy in men that severely influences quality of life. Surgery is most often the recommended treatment for PCa, but radical prostatectomy can cause significant urinary adverse effects. Therefore, finding effective biochemical treatments for PCa remains a necessity. Aurora kinase A has been shown to be involved in PCa progression, thus making it a good target for PCa therapy. miRNAs are important regulators of gene expression, with some miRNAs specifically involved in carcinogenesis. Therefore, herein, we identified miRNAs targeted to aurora kinase A and examined their effects on the growth of PCa. We used primary samples from PCa patients and PCa cell lines as research subjects. We demonstrate that miR-199a-3p is down-regulated in PCa tissues compared with normal prostate tissues, with the expression pattern inversely correlated with the expression pattern of aurora kinase A. We find that miR-199a-3p agomir inhibits aurora kinase A and attenuates xenograft tumor growth of PCa. Moreover, we demonstrate that down-regulation of miR-199a-3p results from enhancement of the methylation of miR-199agene in PCa. Furthermore, we find that the expression level of miR-199a-3p is inversely correlated to tumor stage and Gleason score of PCa. Revealing novel mechanisms for oncogene inhibition by miRNA-mediated pathways offers new avenues for PCa treatment.
Details
- Language :
- English
- ISSN :
- 00029440
- Volume :
- 184
- Issue :
- 5
- Database :
- Supplemental Index
- Journal :
- American Journal of Pathology
- Publication Type :
- Periodical
- Accession number :
- ejs32745123
- Full Text :
- https://doi.org/10.1016/j.ajpath.2014.01.017