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Transcription factor AP-2α regulates acute myeloid leukemia cell proliferation by influencing Hoxa gene expression.
|Title||Transcription factor AP-2α regulates acute myeloid leukemia cell proliferation by influencing Hoxa gene expression.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Ding X, Yang Z, Zhou F, Wang F, Li X, Chen C, Li X, Hu X, Xiang S, Zhang J|
|Journal||The international journal of biochemistry & cell biology|
|Date Published||2013 Aug|
Transcription factor AP-2α mediates transcription of a number of genes implicated in mammalian development, cell proliferation and carcinogenesis. In the current study, we identified Hoxa7, Hoxa9 and Hox cofactor Meis1 as AP-2α target genes, which are involved in myeloid leukemogenesis. Luciferase reporter assays revealed that overexpression of AP-2α activated transcription activities of Hoxa7, Hoxa9 and Meis1, whereas siRNA of AP-2α inhibited their transcription activities. We found that AP-2 binding sites in regulatory regions of three genes activated their transcription by mutant analysis and AP-2α could interact with AP-2 binding sites in vivo by chromatin immunoprecipitation (ChIP). Further results showed that the AP-2α shRNA efficiently inhibited mRNA and protein levels of Hoxa7, Hoxa9 and Meis1 in AML cell lines U937 and HL60. Moreover, decreased expression of AP-2α resulted in a significant reduction in the growth and proliferation of AML cells in vitro. Remarkably, AP-2α knockdown leukemia cells exhibit decreased tumorigenicity in vivo compared with controls. Finally, AP-2α and target genes in clinical acute myeloid leukemia samples of M5b subtype revealed variable expression levels and broadly paralleled expression. These data support a role of AP-2α in mediating the expression of Hoxa genes in acute myeloid leukemia to influence the proliferation and cell survival.
|Alternate Journal||Int. J. Biochem. Cell Biol.|