Table 2. Circulating miRNAs and their impact in PCa.
miRNA | Levels | Role | Therapy Response | Refs. |
---|---|---|---|---|
miR16 miR-26a |
Increased in PCa patients | Not known | Decreased after radical prostatectomy | [71] |
miR1290 miR-375 |
Increased in castration-resistant PCa |
Predicts the overall survival independently from PSA or from the failure time of androgen-deprivation therapy | Not known | [69] |
miR-100 miR-125b miR143 miR-205 miR-296 |
High | Allows discriminating metastatic PCa patients from healthy individuals | Not known | [10] |
miRNA-141 | Differential circulating profile in relation to different stage of PCa | Close to normal in the early stages of PCa but increase dramatically in advanced PCa patients, in parallel with prostate serum antigen levels |
Not known | [71] |
miR-21 | Markedly higher in the early than in the advanced disease stage | Not known | Not known | [10, 72] |
miR-26a miR-16 miR-195 |
Highly relatedwith surgical margin positivity | Not known | Not known | [71] |
miR-195 miR- let7i |
Not determined | Correlates with Gleason score | Not known | [71] |
miR26a miR21 miR-221 miR-151-3p miR-152 miR-205 miR-423-3p miR- 375 miR- let7i, miR-200b miR-195 miR-16 |
Not determined | Provides diagnostic or prognostic informations in patients with clinically localized PCa | Not known | [10] |
and DNMT3b) [80]. The intriguing miR-29 regulation of DNA methylation state has been described firstly in lung cancer, where miR-29 family was shown to be able to target DNA methylases or DNA demethylases [81]. In prostate cancer PC-3 and DU145 cell lines, down-regulation of miR-29s and in particular of miR-29b, has been found to affect focal adhesion pathway, stimulate MMP-2 expression and cell migration via laminin γ1 (LAMC1) gene targeting [82]. The recovery of miR-29b expression in PC-3 cells blocks migration and invasion [83] and EMT transition [37], hampering therefore PCa cells aggressiveness [37]. Notably, in DU145 and in TRAMP-C1 mice, the up-regulation of miR-29b, mediated by the activation of toll-like receptor 3 (TLR3), determines demethylation and restoration of gene expression of the tumor suppressor retinoic acid receptor beta. In formalin-fixed paraffin-embedded tissues of human primary PCa, the down-regulation of miRNA-29b, -29c, -148b, and -152 has also been confirmed [84].