Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Haematologica. 2013 Mar;98(3):414-9. doi: 10.3324/haematol.2012.071753. Epub 2012 Sep 14.
The transcription factor TWIST-1 is up-regulated in CD34(+) cells in myelodysplastic syndrome and is involved in resistance to apoptosis. There is evidence that TWIST-1 affects apoptosis via microRNAs (miRs). Expression of miRs was determined in myeloid cell lines and primary CD34(+) marrow cells from patients with myelodysplastic syndrome and healthy donors using NanoString/array and validated by real-time-polymerase chain reaction. Expression levels of miR10a and miR10b were significantly higher in CD34(+) marrow cells from 28 patients with myelodysplastic syndrome than in CD34(+) cells from healthy donors (P=0.05 and P=0.012, respectively). Levels of miR10a/b correlated with TWIST-1 miR levels in CD34(+) myelodysplastic marrow cells (miR10a, R=+0.69, P<0.0001; miR10b, R=+0.56, P=0.0008). Inhibition of miR10a/10b in clonal cells interfered with proliferation and enhanced sensitivity to apoptosis, which involved NF-κB-dependent p53 activation. These data support a role for miR10a/10b in the regulation of apoptosis in myelodysplastic syndrome and suggest the TWIST-1/miR10a/b-axis as a therapeutic target in myelodysplastic syndrome.
转录因子 TWIST-1 在骨髓增生异常综合征的 CD34(+)细胞中上调，并参与抗细胞凋亡。有证据表明 TWIST-1 通过 microRNAs（miRs）影响细胞凋亡。使用 NanoString/array 在骨髓增生异常综合征患者和健康供体的髓系细胞系和原代 CD34(+)骨髓细胞中确定了 miRs 的表达，并通过实时聚合酶链反应进行了验证。与健康供体的 CD34(+)细胞相比，28 例骨髓增生异常综合征患者的 CD34(+)骨髓细胞中 miR10a 和 miR10b 的表达水平明显更高（分别为 P=0.05 和 P=0.012）。miR10a/b 的水平与 CD34(+)骨髓增生异常细胞中的 TWIST-1 miR 水平相关（miR10a，R=+0.69，P<0.0001；miR10b，R=+0.56，P=0.0008）。在克隆细胞中抑制 miR10a/10b 会干扰增殖并增强对细胞凋亡的敏感性，这涉及 NF-κB 依赖性 p53 激活。这些数据支持 miR10a/10b 在骨髓增生异常综合征中调节细胞凋亡的作用，并表明 TWIST-1/miR10a/b 轴是骨髓增生异常综合征的治疗靶点。
