SOX12: a novel potential target for acute myeloid leukaemia.
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.
['Wan|Haixia|H|', 'Cai|Jiayi|J|', 'Chen|Fangyuan|F|', 'Zhu|Jianyi|J|', 'Zhong|Jihua|J|', 'Zhong|Hua|H|']
D000818:Animals D059447:Cell Cycle Checkpoints D045744:Cell Line, Tumor D005786:Gene Expression Regulation D055785:Gene Knockdown Techniques D064593:Heterografts D006801:Humans D015470:Leukemia, Myeloid, Acute D051379:Mice D016688:Mice, Inbred NOD D012333:RNA, Messenger D055751:SOXC Transcription Factors D051820:TCF Transcription Factors D060449:Wnt Signaling Pathway D051176:beta Catenin
acute myeloid leukaemia leukaemia progression TCF/Wnt SRY-related high-mobility group box 12 leukaemia-initiating cells