HIF-α Promotes Chronic Myelogenous Leukemia Cell Proliferation by Upregulating p21 Expression
HIF-α Promotes Chronic Myelogenous Leukemia Cell Proliferation by Upregulating p21 Expression
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DOI：
10.1007/s12013-014-0434-2
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发表时间：
2015-05-01
影响因子：
2.6
通讯作者：
Zhang, Ri
中科院分区：
文献类型：
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作者：
Chen, Heng;Shen, Yunfeng;Zhang, Ri
我们试图确定缺氧诱导因子-1 α (HIF-1 α)在骨髓慢性髓性白血病（CML）患者中的表达水平。我们还试图通过敲低小干扰RNA （siRNA）来确定HIF-1 α在CML细胞增殖中的作用。采用Real-time PCR检测CML患者和健康志愿者骨髓中HIF-1 α的表达水平。RT-PCR证实K562细胞中HIF-1 α被siRNA敲低。HIF-1 α敲除后，CCK8检测处理细胞的增殖和集落形成。RT-PCR和western blotting检测K562细胞中p21和p53的mRNA和蛋白水平。CML患者骨髓HIF-1 α mRNA表达量显著高于对照组，差异有统计学意义（P < 0.05）。HIF-1 α敲除显著降低K562细胞的增殖，差异亦有统计学意义（P < 0.05）。HIF-1 α敲低显著降低K562细胞集落形成能力，差异亦有统计学意义（P < 0.05）。HIF-1 α敲除后，K562细胞中p21 mRNA和蛋白的表达显著降低，影响p53 mRNA和蛋白的表达水平。hif - α通过上调p21表达促进慢性CML细胞增殖。
We sought to determine the expression levels of hypoxia-inducible factor-1 alpha (HIF-1 alpha) in the bone marrow chronic myelogenous leukemia (CML) patients. We also tried to determine the roles HIF-1 alpha in the proliferation of CML cells by small interfering RNA (siRNA) knockdown. Real-time PCR was performed to determine the expression levels of HIF-1 alpha in the bone marrows of CML patients and healthy volunteers. HIF-1 alpha knockdown by siRNA in K562 cells was confirmed by RT-PCR. Proliferation and colony formation of the treated cells were determined by CCK8 after HIF-1 alpha knockdown. RT-PCR and western blotting were performed to detect mRNA and protein levels of p21 and p53 in K562 cells. HIF-1 alpha mRNA expression in the bone marrow of CML patients was significantly higher than that in the control, which was statistically significant (P < 0.05). HIF-1 alpha knockdown dramatically reduced the proliferation of K562 cells, which was also statistically significant (P < 0.05). HIF-1 alpha knockdown markedly reduced the colony formation ability of K562 cells, which was also statistically significant (P < 0.05). The mRNA and protein expression of p21 were significantly reduced in K562 cell after HIF-1 alpha knockdown with affecting the mRNA and protein levels of p53. HIF-alpha promotes chronic CML cell proliferation by up-regulating p21 expression.