Inhibition of class I histone deacetylases 1 and 2 promotes urothelial carcinoma cell death by various mechanisms (HDAC siRNA knockdown)

Class I histone deacetylases HDAC1 and HDAC2 contribute to cell proliferation and are commonly upregulated in urothelial carcinoma (UC). To evaluate whether specific inhibition of HDAC1 and HDAC2 might serve as an appropriate therapy of UC we applied specific siRNA mediated double knockdown of HDAC1 and HDAC2 in the UCCs VM-CUB1 and UM-UC-3. HDAC1/2 double knockdown significantly reduced proliferation and clonogenicity of UC cells. For differential gene expression analyses independently replicated high quality RNA preparations from VM-CUB1 and UM-UC-3 cells, transfected with HDAC1 and HDAC2 siRNA (72 h), were compared to irrelevant (non-targeting) siRNA control cells.