In the process of assessing the prognostic significance of miR-214, we discovered that bladder cancer patients with low miR-214 expression had a significantly higher recurrence and shorter overall survival after surgery and multivariate analysis identified miR-214 as an independent prognostic factor for RFS and OS in patients with MIBC. Our findings presented that miR-214 dysregulation could serve as a novel prognostic biomarker for MIBC, just as it can be prognosticator in human hepatoma. In addition, urinary levels of cell-free miR-214 have been reported to be an independent prognostic parameter for NMIBC recurrence. Although the use of a large body of bladder tumors with a wide variety of grade and stage in our study, independent validation studies are needed to evaluate the performance of miR-214 before considering its use as potential biomarkers. However, prognostic relevance of postoperative NVP-BEZ235 PI3K inhibitor adjuvant therapy was not explored in this study although it was widely considered helpful for prognosis of bladder cancer. For one thing, there was no uniform therapeutic schedule in all cases according to the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology for bladder cancer; for another, some patients did not receive or failed to complete the adjuvant therapy because of economic pressures or unbearable side effects. In vitro functional studies demonstrated that reexpression of miR-214 in bladder cancer cells induced phenotypes consistent with decreased cellular proliferation, migration and invasion concomitant with increased apoptosis, confirming the tumor-suppressive role of miR-214 in bladder cancer. Apoptosis serves as a LY294002 well-orchestrated natural barrier to cancer pathogenesis and limiting or circumventing apoptosis is generally recognized as one of the major hallmarks of tumorigenesis. Here we demonstrated that miR-214 restoration markedly induced apoptosis, verifying the important proapoptotic role of miR-214. Several miRNAs have also been reported to directly or indirectly regulate apoptosis in bladder cancer. Altogether, the suppressive effects on bladder cancer cell growth and metastasis combined with proapoptotic role of miR-214 might make for the poor prognosis of bladder cancer patients with low expression of miR-214. Integrated bioinformatics analysis recognizes PDRG1 as miR-214 target gene. However, the interaction between miR-214 and PDRG1 has not been reported. Dual-luciferase reporter assay revealed that PDRG1 had a miR-214 binding site in its 30 UTR and PDRG1 was inversely related to miR-214 expression in bladder cancer clinical specimens. Restoration of miR-214 lowered PDRG1 expression in both mRNA and protein levels, suggesting that miR-214 reduce PDRG1 expression by degrading its mRNA.