Figure 6.

PARP1 Promotes KIT Expression by Activating NF-κB-P65 Transcription

Forced expression of PARP1 enhanced P65 protein expression level (A) and downregulated PARP1 expression by olaparib-inhibited P65 protein expression level in K562 cells (B). (C) Forced expression of PARP1 enhanced P65 mRNA expression level and downregulated PARP1 expression by olaparib-inhibited P65 mRNA expression level in K562 cells. Forced expression of P65 enhanced KIT protein expression level (D), and downregulated P65 expression by P65-siRNA transfection inhibited KIT protein expression level in K562 cells (E). (F) Forced expression of P65 enhanced KIT mRNA expression level, and downregulated P65 expression by P65-siRNA transfection inhibited KIT mRNA expression level in K562 cells. (G) Olaparib inhibited the colony-formation abilities of K562 cells with stable overexpression of PPFIA1. (H) Olaparib administered at the dose of 50 mg/kg daily increased survival duration in mice engrafted with Baf3-P210 cells compared with untreated Baf3-P210 cells engrafted controls (n = 7/group). Curves were compared by log rank test (p = 0.0445). (I) Summary diagram describes the function of PPFIA1/PARP1/KIT/NF-κB-P65 network in CML cell lines. The data were presented as the mean ± SD obtained from at least three independent experiments. Significance was determined by Student’s t test, **p < 0.01, *p < 0.05 versus NC control.