Table 1. Models to evaluate the role of HuR in PARPi response.
DDR status |
Cell lines | Olaparib | Veliparib | Rucaparib | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|
IC50 μM |
Fold- change |
P-value (two- tailed) |
IC50 μM |
Fold- change |
P-value (two- tailed) |
IC50 μM |
Fold- change |
P-value (two- tailed) |
|||
CRIPSR knockout | Deficient | HST.HuR(+/+) | 8.30 | 21.8 | >0.0001 | 2.20 | 2.6 | 0.0009 | 4.56 | 12.6 | >0.0001 |
HST.HuR(−/−) | 0.38 | 0.85 | 0.36 | ||||||||
Proficient | MIA.HuR(+/+) | 12.52 | 21.9 | >0.0001 | 12.04 | 15.5 | >0.0001 | 10.22 | 20.8 | >0.0001 | |
MIA.HuR(−/−) | 0.57 | 0.76 | 0.49 | ||||||||
siRNA silencing | Deficient | Capan-1 siCon |
1.28 | 3.5 | >0.0001 | 4.25 | 10.1 | >0.0001 | 10.40 | 5.3 | >0.0001 |
Capan-1 siHuR |
0.36 | 0.42 | 1.95 | ||||||||
Deficient | Hs 766T siCon |
8.40 | 3.8 | >0.0001 | 6.25 | 2.0 | >0.0001 | 9.25 | 2.76 | >0.0001 | |
Hs 766T siHuR |
2.24 | 3.12 | 3.35 | ||||||||
Proficient | MIA PaCa-2 siCon |
13.21 | 6.20 | >0.0001 | 13.32 | 5.3 | >0.0001 | 15.60 | 6.24 | >0.0001 | |
MIA PaCa-2 siHuR |
2.13 | 2.50 | 2.50 | ||||||||
Deficient | Capan-1 (Vehicle) | 1.87 | 3.0 | 0.0009 | 1.20 | 2.1 | 0.0009 | 1.65 | 3.8 | >0.0001 | |
Capan-1 (MS-444) | 0.62 | 0.56 | 0.43 | ||||||||
Small Molecule inhibition (MS-444) | Deficient | Hs 766T (Vehicle) | 4.32 | 2.3 | >0.001 | 3.0 | 4.1 | >0.0001 | 4.18 | 3.2 | >0.001 |
Hs 766T (MS-444) | 1.87 | 0.73 | 1.31 | ||||||||
Proficient | MIA PaCa-2 (Vehicle) | 11.67 | 4.4 | >0.0001 | 12.56 | 4.0 | >0.0001 | 11.88 | 3.2 | 0.0009 | |
MIA PaCa-2 (MS-444) | 2.68 | 3.20 | 3.68 |