Recently, we have identified GSK-3 as a new therapeutic target in renal cell cancer (RCC). miR-199a could potentially downregulate GSK-3β expression. Here, we found a decreased miR-199a expression in 59% (32 of 54) of RCCs and it was correlated with higher tumor stage (p < 0.05) and nuclear overexpression of GSK-3β (p < 0.05). We show that re-expression of miR-199a downregulates GSK-3β and suppresses cancer cell growth. Our results demonstrate low miR-199a expression as a feature of advanced RCCs, identify miR-199a as a negative regulator of GSK-3β, and suggest re-expression of pre-miR-199a as a new potential treatment of RCC.

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