SOX12: a novel potential target for acute myeloid leukaemia
SOX12: a novel potential target for acute myeloid leukaemia
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SOX12：急性髓系白血病的新潜在靶点
DOI：
10.1111/bjh.14425
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发表时间：
2017-02-01
影响因子：
6.5
通讯作者：
Zhong, Hua
中科院分区：
文献类型：
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作者：
Wan, Haixia;Cai, Jiayi;Zhong, Hua
SRY 相关的高迁移率族盒 (SOX) 12 在白血病进展和造血中的作用仍然难以捉摸。本研究旨在利用人髓系白血病样本和急性髓系细胞系 THP1 检测 SOX12 在急性髓系白血病 (AML) 中的表达和功能。从 AML 患者和健康捐赠者的骨髓中分离出单核细胞。通过逆转录聚合酶链反应（RT-PCR）评估造血细胞中的SOX12表达。 SOX12 短发夹 RNA (shRNA) 被转导至 THP1 细胞中，并通过定量 RT-PCR 和蛋白质印迹分析证实基因敲低。 SOX12在AML患者的CD34(+)细胞中优先表达。转导 SOX12 shRNA 的 THP1 细胞表现出显着降低的 SOX12 表达和细胞增殖。 SOX12敲低对细胞凋亡没有影响，但它会诱导细胞周期停滞在G1期并减少集落数量。转导的THP1和原代AML细胞在非肥胖糖尿病-严重联合免疫缺陷(NOD/SCID)小鼠中重建，移植后6-12周其数量显着减少。 SOX12 敲低后，α-连环蛋白的 mRNA 和蛋白水平显着降低，同时 TCF/Wnt 活性降低。 SOX12可能通过调节β-catenin表达进而干扰TCF/Wnt通路参与白血病进展，这可能是AML的靶点。
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 6-12weeks after transplantation. The mRNA and protein levels of -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 -catenin and then interfering with TCF/Wnt pathway, which may be a target for AML.