Gene expression profile analysis of SUDHL6 cells with siRNA‐mediated BCL11A downregulation

Abstract

Our previous study has shown that downregulation of B-cell chronic lymphocytic leukemia (CLL)/lymphoma11A (BCL11A) gene by small interfering RNA (siRNA) resulted in the growth inhibition and apoptosis of B cell lymphoma cell line SUDHL6. To gain further insight into the molecular mechanisms of this process and identify the differentially expressed genes in SUDHL6 cells after BCL11A downregulation, the global gene expression profile was identified and analyzed using the Affymetrix HG-U133 Plus 2.0 array. Twenty-one differentially expressed genes were validated and analyzed from the BCL11A siRNA-treated SUDHL6 cells. There was a significant dysregulation in the global gene expression of the BCL11A-suppressed SUDHL6 cells. There were 1903 genes differentially expressed with >2-fold changes between the BCL11A siRNA- and negative control-transfected cells. Of these, there were 916 upregulated genes and 987 downregulated genes. The differential genes are involved in various molecular functions and signaling pathways. QRT-PCR validation of the selected differentially expressed genes demonstrated there was a good correlation with the microarray analysis. There was a significant deregulation of expression in the apoptosis-related genes such as BCL-2, BCL2L11 and involved in TGFβ, MAPK, WNT signaling pathways after BCL11A was downregulated in SUDHL6 cells. Our results show that the suppression of BCL11A by RNA interference altered gene expression profile of SUDHL6 cells. The apoptosis-related genes BCL-2, BCL2L11 and the gene alterations in TGFβ, MAPK, WNT signaling pathways might be important in BCL11A siRNA-induced apoptosis of SUDHL6 cells, suggesting BCL11A is involved in gene networks associated with apoptosis.

Sex differences in the genome-wide DNA methylation pattern and impact on gene expression, microRNA levels and insulin secretion in human pancreatic islets

“…BCL11A encodes B-cell CLL/lymphoma 11A, a zinc finger protein essential for lymphoid development [ 61 , 62 ] as it controls the expression and activity of Bcl2 , Bcl2-xL , Mdm2 and p53 and thereby cell survival. Furthermore, knockdown of BCL11A leads to increased rates of apoptosis in lymphoma cell lines [ 63 - 65 ]. Possibly, reduced BCL11A expression could also affect survival of other cell types, including β-cells, and thereby diabetes risk.…”

SWI/SNF complexes in hematological malignancies: biological implications and therapeutic opportunities

“…BCL11A is a zinc-finger transcription factor highly expressed in several hematopoietic lineages. It has been observed that BCL11A may induce the cell cycle progression of hematopoietic cells by directly inhibiting p21 expression [ 95 ], and it may deregulate the expression of a plethora of genes involved in apoptosis [ 107 ] or those regulated by other myeloid tumor suppressors such as PU.1 [ 94 ].…”

BCL11A: a potential diagnostic biomarker and therapeutic target in human diseases

“…Still by retroviral insertion screening, BCL11A was identified to accelerate the process of AML caused by t(9;11) translocation by cooperating with MLL-AF9 [26]. Wu et al [77] furtherly analyzed the global gene expression profile, the results showed that BCL11A may inhibit the apoptosis of B-cell lymphoma cell line through the transforming growth factor-β (TGFβ), mitogen-activated protein kinase (MAPK), and Wingless/Integrated (WNT) signaling pathways. It is noteworthy that knockdown of BCL11A mRNA by small interfering RNA combined with vincristine can decrease cell proliferation and increase cell apoptosis in B-cell lymphoma [78].…”