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Our recent study of the micro RNA  (mi RNA ) expression signature of bladder cancer ( BC ) by deep‐sequencing revealed that two mi RNA ,  micro RNA ‐139‐5p / micro RNA ‐139‐3p  were significantly downregulated in  BC  tissues. The aim of this study was to investigate the functional roles of these mi RNA  and their modulation of cancer networks in  BC  cells. Functional assays of  BC  cells were performed using transfection of mature mi RNA  or small interfering  RNA  (si RNA ). Genome‐wide gene expression analysis,  in silico  analysis and dual‐luciferase reporter assays were applied to identify mi RNA  targets. The associations between the expression of mi RNA  and its targets and overall survival were estimated by the Kaplan–Meier method. Gain‐of‐function studies showed that  miR‐139‐5p  and  miR‐139‐3p  significantly inhibited cell migration and invasion by  BC  cells. The matrix metalloprotease 11 gene (  MMP 11 ) was identified as a direct target of  miR‐139‐5p  and  miR‐139‐3p . Kaplan–Meier survival curves showed that higher expression of   MMP 11  predicted shorter survival of  BC  patients ( P =  0.029). Downregulated  miR‐139‐5p  or  miR‐139‐3p  enhanced  BC  cell migration and invasion in  BC  cells.   MMP 11  was directly regulated by these mi RNA  and might be a good prognostic marker for survival of  BC  patients.

Dual tumor‐suppressors miR‐139‐5p and miR‐139‐3p targeting matrix metalloprotease 11 in bladder cancer