title: SOX12: a novel potential target for acute myeloid leukaemia.
abstract: The role of SRY-related high-mobility-group box (SOX) 12 in leukaemia progression and haematopoiesis remains elusive. This study aimed to examine the expression and function of SOX12 in acute myeloid leukaemia (AML) using human myeloid leukaemia samples and the acute myeloid cell line THP1. Mononuclear cells were isolated from the bone marrow of AML patients and healthy donors. SOX12 expression in haematopoietic cells was evaluated by reverse transcription polymerase chain reaction (RT-PCR). SOX12 short hairpin RNAs (shRNAs) were transduced into THP1 cells, and gene knockdown was confirmed by quantitative RT-PCR and Western blot analysis. SOX12 was preferentially expressed in CD34+cells in AML patients. The THP1 cells transduced with SOX12 shRNAs exhibited significantly reduced SOX12 expression and cell proliferation. SOX12 knockdown had no effect on apoptosis, but it induced cell cycle arrest at G1 phase and reduced the number of colonies. The transduced THP1 and primary AML cells were reconstituted in non-obese diabetic-severe combined immunodeficient (NOD/SCID) mice, and their numbers were significantly reduced 6-12 weeks after transplantation. The mRNA and protein levels of β-catenin were significantly diminished following SOX12 knockdown, accompanied by a decrease in TCF/Wnt activity. SOX12 may be involved in leukaemia progression by regulating the expression of β-catenin and then interfering with TCF/Wnt pathway, which may be a target for AML.
authors.affiliation: Department of Haematology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Haixia
authors.initials: H
authors.lastname: Wan
authors.affiliation: Department of Haematology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Haematology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Chen
authors.affiliation: Department of Haematology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jianyi
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Haematology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jihua
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Department of Haematology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhong
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016688:Mice, Inbred NOD; D012333:RNA, Messenger / Q000032:analysis; D055751:SOXC Transcription Factors / Q000235:genetics* / Q000494:pharmacology; D051820:TCF Transcription Factors / Q000187:drug effects / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000032:analysis / Q000187:drug effects / Q000235:genetics
chemical_list: D012333:RNA, Messenger; C107423:SOX12 protein, human; D055751:SOXC Transcription Factors; D051820:TCF Transcription Factors; D051176:beta Catenin
keywords: SRY-related high-mobility group box 12; TCF/Wnt; acute myeloid leukaemia; leukaemia progression; leukaemia-initiating cells