Fig. 6

Knockdown of Sirt6 inhibited activation of PI3K/Akt/mTOR signaling pathway. a GSEA according to the RNA-seq implicated that Sirt6 was functionally enriched in the PI3K/Akt signaling pathway and FoxO signaling pathway. b Western blot was conducted to assess the phosphorylated (p) and total (t) protein levels of PI3K signaling cascades. PI3K p110α and its downstream targets, including Akt (Ser473) and mTOR protein, were observed to be dramatically decreased in Sirt6 knockdown cells in comparison to control cells. The tumor suppressor FoxO1 protein increased in shSirt6 cells. c Decreased activation of PI3K signaling was observed in shSirt6-treated mice. d IGF-1-induced DLBCL cell (LY1 and LY8) proliferation is inhibited by Sirt6-depletion. e LY1 cell transfected with shSirt6 or shControl, serum starved for 48 h, and treated with IGF-1. Decreased activation of PI3K signaling was observed in sh-Sirt6-treated cell. f Schematic description of Sirt6 mediated PI3K, FoxO, and DNA damage signaling