Fig. 7: YAP1/AKT axis is essential for ANKHD1/MALAT1-mediated radioresistance of CRC cells.

A Overexpression of YAP1 abrogated radiosensitivity in sh-ANKHD1 or sh-MALAT1 cells. B, H Overexpression of YAP1 reduced the large number of γH2AX foci induced by ANKHD1 silencing or MALAT1 silencing at 0.5 h post IR (**P < 0.01). C γH2AX was also tested by Western blotting at 0, 0.5, 4, and 12 h post IR. D Overexpression of YAP1 decreased the formation of ROS caused by ANKHD1 silencing or MALAT1 silencing at 0.5 h post IR (*P < 0.05). E Overexpression of YAP1 recovered the expression of p-ATM, 53BP1, RAD50, MRE11, NBS1, and p-CHK2 in ANKHD1-silenced cells or MALAT1-silenced cells after 0.5- and 4-Gy IR. F ANKHD1 silencing inhibited the activation of the PI3K/AKT signaling pathway with or without IR. G Overexpression of YAP1 reactivated the PI3K/AKT signaling pathway. H, I Treatment with the PI-3 kinase inhibitor LY294002 abrogated the effect of YAP1 on the expression of γH2AX in sh-ANKHD1 or sh-MALAT1 cells. J Western blot results showed that inactivation of AKT caused by LY294002 markedly decreased YAP1-induced upregulation of MRE11 and phosphorylation of the checkpoint protein CHK2 at 0.5 and 4 h post IR.