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HERG钾通道表达增加促进骨髓增生异常综合征进展,并与预后分层相关。

Increased expression of HERG K channels contributes to myelodysplastic syndrome progression and displays correlation with prognosis stratification.

作者信息

Lu Li, Du Wen, Liu Wei, Guo Dongmei, He Xiaoqi, Li Huiyu

机构信息

a Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.

出版信息

Hematology. 2016 Dec;21(10):583-592. doi: 10.1080/10245332.2016.1151603. Epub 2016 Mar 16.

Abstract

OBJECTIVES

Human ether-a-go-go-related gene (HERG) K channels are shown to be aberrantly expressed in a variety of cancer cells where they play roles in contributing to cancer progression. Myelodysplastic syndromes (MDS) are a group of clinical heterogeneous disorders characterized by bone marrow failure and dysplasia of blood cells. However, the involvement of HERG K channels in MDS development is poorly understood.

METHODS

The expression of HERG K channels in untreated MDS, acute myeloid leukemia (AML) patients and the control group was detected by flow cytometry. The roles of HERG K channels in regulation of SKM-1 cell proliferation, apoptosis, and cell cycle were determined by CCK-8 assay and flow cytometry, respectively.

RESULTS

We found that expression of HERG K channels in MDS patients was significantly higher than controls and was lower than AML. Percentage of HERG K channels on CD34+CD38- cells gradually increased from controls to high-grade MDS subtypes. And HERG K channel levels showed an ascending tendency from low-risk to high-risk MDS group. In addition, the CCK-8 assay, apoptosis and cell cycle analysis were performed and showed that blockage of HERG K channels decreased the proliferation of MDS cells but rarely had effects on cell apoptosis and cell cycle distribution.

CONCLUSION

Our study demonstrated that HERG K channels might be a potential tumor marker of MDS. These channels were likely to contribute to MDS progression and were helpful for predicting prognosis of MDS. Inhibition of HERG K channels might be a novel therapeutic measure for MDS.

摘要

目的

人醚 - 去极化相关基因(HERG)钾通道在多种癌细胞中异常表达,在癌症进展中发挥作用。骨髓增生异常综合征(MDS)是一组临床异质性疾病,其特征为骨髓衰竭和血细胞发育异常。然而,HERG钾通道在MDS发生发展中的作用尚不清楚。

方法

采用流式细胞术检测未经治疗的MDS、急性髓系白血病(AML)患者及对照组中HERG钾通道的表达。分别通过CCK - 8法和流式细胞术确定HERG钾通道对SKM - 1细胞增殖、凋亡和细胞周期的调控作用。

结果

我们发现MDS患者中HERG钾通道的表达显著高于对照组且低于AML。CD34 + CD38 - 细胞上HERG钾通道的百分比从对照组到高级别MDS亚型逐渐增加。并且HERG钾通道水平从低危到高危MDS组呈上升趋势。此外,进行了CCK - 8检测、凋亡和细胞周期分析,结果显示阻断HERG钾通道可降低MDS细胞的增殖,但对细胞凋亡和细胞周期分布影响较小。

结论

我们的研究表明HERG钾通道可能是MDS的潜在肿瘤标志物。这些通道可能促进MDS进展,有助于预测MDS的预后。抑制HERG钾通道可能是MDS的一种新型治疗措施。

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