[No authors listed]
miRNAâ223 (miRâ223) has been reported to function not only as a tumor suppressor, but also as an oncogenic microRNA (miRNA or miR) in various cancer cells. Therefore, the functional role of miRâ223 has not been elucidated to date, at least to the best of our knowledge. We previously performed the deep sequencing analysis of clinical bladder cancer (BC) specimens. It was revealed that miRâ223 expression was significantly downregulated in BC, suggesting that miRâ223 functions as a tumor suppressor miRNA in BC. The aim of this study was to investigate the functional roles of miRâ223 and to identify its targets in BC. The expression levels of miRâ223 were significantly decreased in our clinical BC specimens. The Cancer Genome Atlas (TCGA) database indicated that miRâ223 expression was related to lymphovascular invasion and distant metastasis. The restoration of miRâ223 expression significantly inhibited tumor aggressiveness and induced apoptosis via caspaseâ3/7 activation in BC cells. WD repeat domain 62 (WDR62), a candidate target of miRâ223 according to in silico analyses, has been previously proposed to play a role in neurodevelopment. Direct binding between WDR62 and miRâ223 was confirmed by luciferase assay. The TCGA database revealed positive associations between WDR62 mRNA expression and a higher tumor grade and stage in BC. The knockdown of WDR62 significantly inhibited tumor aggressiveness and induced the apoptosis of BC cells. On the whole, the findings of this study reveal a novel miRâ223 target, oncogenic WDR62, and provided insight into the oncogenesis of BC.
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