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Gene expression profiles in BCL11B-siRNA treated malignant T cells.

Huang X, Shen Q, Chen S, Chen S, Yang L, Weng J, Du X, Grabarczyk P, Przybylski GK, Schmidt CA, Li Y - J Hematol Oncol (2011)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Hematology, Medical College, Jinan University, Guangzhou, PR China. yangqiuli@hotmail.com

ABSTRACT

Background: Downregulation 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.

Results: 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. 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.

Conclusion: BCL11B-siRNA treatment altered expression profiles of TNFSF10, BCL2L1, and SPP1 in both Molt-4 T cell line and primary T-ALL cells.

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Schematic model of the molecular mechanism of BCL11B-siRNA-mediated apoptosis in Molt-4 cell [modified from reference 20].
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Figure 2: Schematic model of the molecular mechanism of BCL11B-siRNA-mediated apoptosis in Molt-4 cell [modified from reference 20].

Mentions: Among apoptosis-related genes, changes in expression levels occurred mainly in three pro-apoptotic genes; TNFSF10, BCL-2 interacting killer (BIK), and BCL-2/E1B 19 kDa interacting protein 3 (BNIP3), which were upregulated 2-4 fold, and one anti-apoptotic gene (BCL2L1) was downregulated by 3-4 fold. The expression levels of SPP1 and CREBBP genes involved in the transforming growth factor (TGF-β) pathway were down by 16 fold. The changes in the expression levels of the TNFSF10, BCL2L1, SPP1, and CREBBP genes were further detected by real-time PCR (Figure 1E). The BH3-only domain proteins BIK and BNIP3, which were located upstream of BCL-2 (Figure 2), may enhance their binding to BCL-2, thereby inhibiting the anti-apoptotic function. Thus, we analyzed the BCL-2 protein expression level by flow cytometry in Molt-4 cells at 72 h after BCL11B-siRNA treatment (Figure 1F). A similar altered expression pattern of these genes, as well as expression of the BCL-2 protein, was confirmed. However, CREBBP did not show downregulation in BCL11B-siRNA treated Molt-4 cells.


Gene expression profiles in BCL11B-siRNA treated malignant T cells.

Huang X, Shen Q, Chen S, Chen S, Yang L, Weng J, Du X, Grabarczyk P, Przybylski GK, Schmidt CA, Li Y - J Hematol Oncol (2011)

Schematic model of the molecular mechanism of BCL11B-siRNA-mediated apoptosis in Molt-4 cell [modified from reference 20].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3113752&req=5

Figure 2: Schematic model of the molecular mechanism of BCL11B-siRNA-mediated apoptosis in Molt-4 cell [modified from reference 20].
Mentions: Among apoptosis-related genes, changes in expression levels occurred mainly in three pro-apoptotic genes; TNFSF10, BCL-2 interacting killer (BIK), and BCL-2/E1B 19 kDa interacting protein 3 (BNIP3), which were upregulated 2-4 fold, and one anti-apoptotic gene (BCL2L1) was downregulated by 3-4 fold. The expression levels of SPP1 and CREBBP genes involved in the transforming growth factor (TGF-β) pathway were down by 16 fold. The changes in the expression levels of the TNFSF10, BCL2L1, SPP1, and CREBBP genes were further detected by real-time PCR (Figure 1E). The BH3-only domain proteins BIK and BNIP3, which were located upstream of BCL-2 (Figure 2), may enhance their binding to BCL-2, thereby inhibiting the anti-apoptotic function. Thus, we analyzed the BCL-2 protein expression level by flow cytometry in Molt-4 cells at 72 h after BCL11B-siRNA treatment (Figure 1F). A similar altered expression pattern of these genes, as well as expression of the BCL-2 protein, was confirmed. However, CREBBP did not show downregulation in BCL11B-siRNA treated Molt-4 cells.

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Hematology, Medical College, Jinan University, Guangzhou, PR China. yangqiuli@hotmail.com

ABSTRACT

Background: Downregulation 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.

Results: 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. 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.

Conclusion: BCL11B-siRNA treatment altered expression profiles of TNFSF10, BCL2L1, and SPP1 in both Molt-4 T cell line and primary T-ALL cells.

Show MeSH
Related in: MedlinePlus