Abstract
BackgroundDownregulation of the B-cell chronic lymphocytic leukemia (CLL)/lymphoma11B (BCL11B) gene by small interfering RNA (siRNA) leads to growth inhibition and apoptosis of the human T-cell acute lymphoblastic leukemia (T-ALL) cell line Molt-4. To further characterize the molecular mechanism, a global gene expression profile of BCL11B-siRNA -treated Molt-4 cells was established. The expression profiles of several genes were further validated in the BCL11B-siRNA -treated Molt-4 cells and primary T-ALL cells.Results142 genes were found to be upregulated and 109 genes downregulated in the BCL11B-siRNA -treated Molt-4 cells by microarray analysis. Among apoptosis-related genes, three pro-apoptotic genes, TNFSF10, BIK, BNIP3, were upregulated and one anti-apoptotic gene, BCL2L1 was downregulated. Moreover, the expression of SPP1 and CREBBP genes involved in the transforming growth factor (TGF-β) pathway was down 16-fold. Expression levels of TNFSF10, BCL2L1, SPP1, and CREBBP were also examined by real-time PCR. A similar expression pattern of TNFSF10, BCL2L1, and SPP1 was identified. However, CREBBP was not downregulated in the BLC11B-siRNA -treated Molt-4 cells.ConclusionBCL11B-siRNA treatment altered expression profiles of TNFSF10, BCL2L1, and SPP1 in both Molt-4 T cell line and primary T-ALL cells.
Highlights
Downregulation of the B-cell chronic lymphocytic leukemia (CLL)/lymphoma11B (BCL11B) gene by small interfering RNA leads to growth inhibition and apoptosis of the human T-cell acute lymphoblastic leukemia (T-ALL) cell line Molt-4
Global gene expression profile in BCL11B-siRNA935 treated Molt-4 cells To determine the molecular mechanisms of BCL11B small interfering RNA (siRNA)-mediated cell apoptosis, global gene expression profiling was performed at 24 h post-transfection, when BCL11B mRNA was most effectively suppressed
Principal component analysis indicated that the changes in the Molt-4 cell gene expression profile could be accounted for primarily by the BCL11B siRNA935 treatment (Figure 1B)
Summary
142 genes were found to be upregulated and 109 genes downregulated in the BCL11B-siRNA -treated Molt-4 cells by microarray analysis. Among apoptosis-related genes, three pro-apoptotic genes, TNFSF10, BIK, BNIP3, were upregulated and one anti-apoptotic gene, BCL2L1 was downregulated. The expression of SPP1 and CREBBP genes involved in the transforming growth factor (TGF-b) pathway was down 16-fold. Expression levels of TNFSF10, BCL2L1, SPP1, and CREBBP were examined by real-time PCR. A similar expression pattern of TNFSF10, BCL2L1, and SPP1 was identified. CREBBP was not downregulated in the BLC11B-siRNA -treated Molt-4 cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
