Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
Biomed Res Int. 2017;2017:9496058. doi: 10.1155/2017/9496058. Epub 2017 Nov 28.
Fetal hemoglobin (HbF; ) is a potent genetic modifier of the severity of -thalassemia and sickle cell anemia. Differences in the levels of HbF that persist into adulthood affect the severity of sickle cell disease and the -thalassemia syndromes. Sry type HMG box (SOX6) is a potent silencer of HbF. Here, we reactivated -globin expression by downregulating SOX6 to alleviate anemia in the -thalassemia patients.
SOX6 was downregulated by lentiviral RNAi (RNA interference) in K562 cell line and an culture model of human erythropoiesis in which erythroblasts are derived from the normal donor mononuclear cells (MNC) or -thalassemia major MNC. The expression of -globin was analyzed by qPCR (quantitative real-time PCR) and WB (western blot).
Our data showed that downregulation of SOX6 induces -globin production in K562 cell line and human erythrocytes from normal donors and -thalassemia major donors, without altering erythroid maturation.
This is the first report on -globin induction by downregulation of SOX6 in human erythroblasts derived from -thalassemia major.
胎儿血红蛋白（HbF）是 - 地中海贫血和镰状细胞贫血严重程度的有力遗传修饰因子。成人期持续存在的 HbF 水平差异会影响镰状细胞病和 - 地中海贫血综合征的严重程度。Sry 型 HMG 盒（SOX6）是 HbF 的有效沉默子。在这里，我们通过下调 SOX6 来重新激活 - 珠蛋白表达，从而减轻 - 地中海贫血患者的贫血。
通过慢病毒 RNAi（RNA 干扰）在 K562 细胞系和人红细胞生成的培养模型中下调 SOX6，该模型中红细胞由正常供体单核细胞（MNC）或 - 重型地中海贫血 MNC 衍生而来。通过 qPCR（实时定量 PCR）和 WB（western blot）分析 - 珠蛋白的表达。
我们的数据表明，下调 SOX6 可诱导 K562 细胞系和来自正常供体和 - 重型地中海贫血供体的人红细胞中的 - 珠蛋白产生，而不改变红细胞成熟。
这是首例关于通过下调 SOX6 在 - 重型地中海贫血衍生的人红细胞中诱导 - 珠蛋白的报道。
