Fig. 6

The AKT2/FOXO3A axis mediates the regulatory function of LIN28B on BIM expression. BIM protein level was detected by western blotting in TOV-112D cells with combined LIN28B knockdown and AKT2 overexpression. b BIM protein level was examined by western blotting in A2780 and TOV-112D cells with combined LIN28B knockdown and FOXO3A knockdown. c BIM mRNA level was detected by q-PCR upon AKT2 overexpression in TOV-112D (LIN28B shRNA) and upon FOXO3A knockdown in A2780 (LIN28B shRNA) and TOV-112D (LIN28B shRNA) cells. Representative results from three independent experiments were shown. *p < 0.05. d The mechanism governing the regulation of apoptosis by LIN28B through the AKT2/FOXO3A/BIM axis. Left: in cancer cells with a high expression level of LIN28B, the LIN28B protein associates with AKT2 mRNA and enhances its translation efficiency. AKT2 phosphorylates FOXO3A and blocks the nuclear translocation of FOXO3A, which results in transcriptional silencing of the BIM gene and resistance to cellular apoptosis. Right: in cancer cells with a low expression level of LIN28B, the translation of AKT2mRNA is decreased. Phosphorylation of FOXO3A by AKT2 is also diminished. The nuclear translocation of FOXO3A leads to transcriptional activation of the BIM gene and cellular apoptosis