title: Transcription factor AP-2α regulates acute myeloid leukemia cell proliferation by influencing Hoxa gene expression.
abstract: 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.
authors: Key Laboratory of Protein Chemistry and Development Biology of State Education Ministry of China, College of Life Science, Hunan Normal University, Changsha 410081, PR China.
authors: Xiaofeng
authors: X
authors: Ding
authors: Zijian
authors: Z
authors: Yang
authors: Fangliang
authors: F
authors: Zhou
authors: Fangmei
authors: F
authors: Wang
authors: Xinxin
authors: X
authors: Li
authors: Cheng
authors: C
authors: Chen
authors: Xiaofeng
authors: X
authors: Li
authors: Xiang
authors: X
authors: Hu
authors: Shuanglin
authors: S
authors: Xiang
authors: Jian
authors: J
authors: Zhang
mesh_terms: D000328:Adult; D000818:Animals; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D047369:Chromatin Immunoprecipitation; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000473:pathology*; D008156:Luciferases / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D050656:Transcription Factor AP-2 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: C115962:HOXA7 protein, human; D018398:Homeodomain Proteins; C000616391:MEIS1 protein, human; C000616392:Meis1 protein, mouse; D000075064:Myeloid Ecotropic Viral Integration Site 1 Protein; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D050656:Transcription Factor AP-2; C097899:homeobox protein HOXA9; D008156:Luciferases
keywords: AML; AP-2α; Hoxa7; Hoxa9; Meis1