PDRG1 knockdown recapitulated the effects of miR-214 overexpression, further illustrating that the anti-tumor role of miR-214 may be mediated primarily via oncogene PDRG1. Additionally, our results showed that PDRG1 promoted bladder cancer cell proliferation and metastasis, while restrained apoptosis. To sum up, these findings suggest that miR-214 regulate PDRG1 to exert its tumor-suppressive effects. Thus far, miR-214-mediated regulation of PDRG1 has not been reported before and is a discovery of particular importance as the rarely studied PDRG1 could involve in regulating cellular stress response, cancer development and progress. PDRG1, namely p53 and DNA damage-regulated gene, resides at the long arm of chromosome 20 and encodes a protein of 133 amino acids presenting within a distinct subcellular compartment in the cytoplasm. p53 could downregulate PDRG1 expression while genotoxic stress upregulate PDRG1 expression in a p53-independent manner. It has been reported recently that PDRG1 expression was upregulated in multiple malignancies including cancers of the colon, rectum, ovary, lung, stomach, breast and uterus compared to their respective matched normal tissues and PDRG1 knockdown in human colon cancer cells resulted in marked slowdown of tumor cell growth, which is in line with our findings. Our study also indicated that up-regulated PDRG1 expression was significantly correlated with higher tumor stage, higher lymph node status and higher grade, suggesting it has the potential to be a novel valuable tumor biomarker that could play a role in bladder cancer development and/or progression. A limitation to this study was that we were unable to carry out an in vivo study and further mouse xenograft model will be conducive to inspecting the therapeutic value of miR-214 in bladder cancer. In conclusion, this is the first report elaborating that miR-214, whose attenuated expression in bladder cancer tissues is associated with worse prognosis, functions as a tumor suppressor by negatively regulating oncogene PDRG1 expression. These findings enrich our understanding of the crucial roles of dysregulated miRNAs in molecular pathogenesis of bladder cancer and provide novel insights into developing potential alluring targets for prognostic and therapeutic interventions in bladder cancer. c-Secretase has been extensively studied as it catalyzes the final step in generation of the neurotoxic amyloid b-peptide, which is involved in the development of Alzheimer disease. It is composed of the four protein subunits presenilin 1 or 2, nicastrin, ONX-0914 960374-59-8 anterior pharynx-defective phenotype 1 and BAY 43-9006 PSenhancer 2. PS1 and PS2 contain nine transmembrane domains of which TM regions six and seven contain two well-conserved aspartyl residues that are required for c-secretase activity. Nicastrin is a type 1 TM protein containing a large and highly glycosylated ectodomain and several studies indicate that nicastrin is involved in substrate selection.