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Previous research evidence suggests that microRNAs (miRNAs) play an indispensable role in onset and progression of bladder cancer (BCa). Here, we explored the functions and mechanisms of miR-5581-3p in BCa. miR-5581-3p, as a tumor suppressor in BCa, was detected at a lower expression level in BCa tissue and cells in contrast with the non-malignant bladder tissue and cells. Over-expression of miR-5581-3p remarkably dampened the migration and proliferation of BCa in vitro and in vivo. SMAD3 and FTO were identified as the direct targets of miR-5581-3p by online databases prediction and mRNA-seq, which were further verified. SMAD3 as a star molecule in modulating EMT progress of BCa had been formulated in former studies. Meanwhile, FTO proved as an N6-methyladenosine (m 6 A) demethylase in decreasing m 6 A modification was confirmed to regulate the migration and proliferation in BCa. In addition, we conducted rescue experiments and confirmed overexpressing miR-5581-3p partially rescued the effects of the overexpressing SMAD3 and FTO in BCa cells. In conclusion, our studies exhibit that miR-5581-3p is a novel tumor inhibitor of BCa.

SMAD3 and FTO are involved in miR-5581-3p-mediated inhibition of cell migration and proliferation in bladder cancer