Little knockdown but big effect on proliferation - (Jul/24/2012 )
Assuming the change is proliferation is not due to the moderate knockdown of your intended target, then perhaps it is the interaction of your knockdown reagent with an unintended RNA (an off-target knockdown) that is causing the change in proliferation.
I agree with the earlier post. It could also be that your GOI is upstream of something else and the moderate reduction is amplified downstream leading to the phenotype that you observed. If you are sure that it can't be due to the knockdown, then the most probable reason is off target effect.