microRNA-mediated resistance to hypoglycemia in the HepG2 human hepatoma cell line.

microRNA-mediated resistance to hypoglycemia in the HepG2 human hepatoma cell line.
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DOI:
10.1186/s12885-016-2762-7
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发表时间:
2016-09-15
期刊:
影响因子:
3.8
通讯作者:
Saito H
Saito H
中科院分区:
医学2区
文献类型:
--
作者:
Ueki S;Murakami Y;Yamada S;Kimura M;Saito Y;Saito H

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一般认为,癌细胞的能量来源依赖于无氧代谢或糖酵解系统,即使它们有足够的氧气。这被称为瓦尔堡效应。当环境发生变化时,细胞在低血糖条件下巧妙地存活,这可能至少部分涉及microRNA(miRNA)介导的调节。为了确定癌细胞如何利用miRNA介导的表观遗传机制在低血糖条件下生存,我们使用DNA微阵列分析来全面并同时比较HepG 2人肝癌细胞系和培养的正常人肝细胞中miRNA和mRNA的表达。低血糖条件降低了肝癌细胞中miRNA-17- 5 p和-20a-5p的表达,从而上调了其靶基因p21的表达。这些调节也通过使用这些miRNAs的反义抑制剂得到证实。除了这种变化,低血糖条件下导致上调表达的热休克蛋白和增加的抵抗caspase-3诱导的细胞凋亡。然而,我们不能确定miRNA介导的调节,尽管使用全面的检测。微阵列分析还发现几个有趣的基因在低血糖条件下上调,可能是因为对这种细胞应激的反应。这些结果表明,癌细胞在低血糖条件下巧妙地存活,这在恶性肿瘤中经常发生,并且该过程的一些基因调控是由miRNA操纵的。本文的在线版本(doi:10.1186/s12885-016-2762-7)包含补充材料,可供授权用户使用。
It is generally accepted that the energy resources of cancer cells rely on anaerobic metabolism or the glycolytic system, even if they have sufficient oxygen. This is known as the Warburg effect. The cells skillfully survive under hypoglycemic conditions when their circumstances change, which probably at least partly involves microRNA (miRNA)-mediated regulation. To determine how cancer cells exploit miRNA-mediated epigenetic mechanisms to survive in hypoglycemic conditions, we used DNA microarray analysis to comprehensively and simultaneously compare the expression of miRNAs and mRNAs in the HepG2 human hepatoma cell line and in cultured normal human hepatocytes. The hypoglycemic condition decreased the expression of miRNA-17-5p and -20a-5p in hepatoma cells and consequently upregulated the expression of their target gene p21. These regulations were also confirmed by using antisense inhibitors of these miRNAs. In addition to this change, the hypoglycemic condition led to upregulated expression of heat shock proteins and increased resistance to caspase-3-induced apoptosis. However, we could not identify miRNA-mediated regulations, despite using comprehensive detection. Several interesting genes were also found to be upregulated in the hypoglycemic condition by the microarray analysis, probably because of responding to this cellular stress. These results suggest that cancer cells skillfully survive in hypoglycemic conditions, which frequently occur in malignancies, and that some of the gene regulation of this process is manipulated by miRNAs. The online version of this article (doi:10.1186/s12885-016-2762-7) contains supplementary material, which is available to authorized users.
Zeste同源物2(EZH2)增强子的抑制剂激活人类癌细胞中的肿瘤抑制剂。
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