一种新型酰基亚精胺类似物- n4 -芥酰亚精胺在Jurkat细胞中释放信号通路的鉴定。

IF 3.2 Q2 GENETICS & HEREDITY
Epigenetics Insights Pub Date : 2018-11-27 eCollection Date: 2018-01-01 DOI:10.1177/2516865718814543
Syed Shoeb Razvi, Hani Choudhry, Mohammed Nihal Hasan, Mohammed A Hassan, Said Salama Moselhy, Khalid Omer Abualnaja, Mazin A Zamzami, Taha Abduallah Kumosani, Abdulrahman Labeed Al-Malki, Majed A Halwani, Abdulkhaleg Ibrahim, Ali Hamiche, Christian Bronner, Tadao Asami, Mahmoud Alhosin
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引用次数: 5

摘要

腐胺、亚精胺、精胺等天然多胺在真核生物的细胞增殖和维持中起着至关重要的作用。然而,肿瘤细胞对多胺的需求增加以维持致瘤性。近年来,人们设计了许多合成的多胺类似物,以多胺在肿瘤中的代谢为靶点,诱导细胞凋亡。N4-Erucoyl亚精胺(设计为N4-Eru)是一种新型的酰基亚精胺衍生物,已被证明对血液和实体肿瘤均有选择性抑制作用,但其作用机制尚不清楚。本研究通过RNA测序研究n4 - eru处理的t细胞急性淋巴细胞白血病(ALL)细胞系(Jurkat细胞)的抗癌机制,并通过不同的工具检测基因表达。我们发现NDRG1、CACNA1G、TGFBR2、NOTCH1、2,3、UHRF1、DNMT1、3、HDAC1、3、KDM3A、KDM4B、KDM4C、FOS和SATB1等关键癌基因下调,而CDKN2AIPNL、KISS1、DDIT3、TP53I13、PPARG、FOXP1等肿瘤抑制基因上调。通过RNA-Seq获得的数据进一步表明,N4-Eru抑制NOTCH/Wnt/JAK-STAT轴。该研究还表明,n4 - eru诱导的细胞凋亡可能涉及癌症的几个关键信号通路。总之,我们的结果表明N4-Eru是一种治疗ALL的有希望的药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Identification of Deregulated Signaling Pathways in Jurkat Cells in Response to a Novel Acylspermidine Analogue-N<sup>4</sup>-Erucoyl Spermidine.

Identification of Deregulated Signaling Pathways in Jurkat Cells in Response to a Novel Acylspermidine Analogue-N<sup>4</sup>-Erucoyl Spermidine.

Identification of Deregulated Signaling Pathways in Jurkat Cells in Response to a Novel Acylspermidine Analogue-N<sup>4</sup>-Erucoyl Spermidine.

Identification of Deregulated Signaling Pathways in Jurkat Cells in Response to a Novel Acylspermidine Analogue-N4-Erucoyl Spermidine.

Natural polyamines such as putrescine, spermidine, and spermine are crucial in the cell proliferation and maintenance in all the eukaryotes. However, the requirement of polyamines in tumor cells is stepped up to maintain tumorigenicity. Many synthetic polyamine analogues have been designed recently to target the polyamine metabolism in tumors to induce apoptosis. N4-Erucoyl spermidine (designed as N4-Eru), a novel acylspermidine derivative, has been shown to exert selective inhibitory effects on both hematological and solid tumors, but its mechanisms of action are unknown. In this study, RNA sequencing was performed to investigate the anticancer mechanisms of N4-Eru-treated T-cell acute lymphoblastic leukemia (ALL) cell line (Jurkat cells), and gene expression was examined through different tools. We could show that many key oncogenes including NDRG1, CACNA1G, TGFBR2, NOTCH1,2,3, UHRF1, DNMT1,3, HDAC1,3, KDM3A, KDM4B, KDM4C, FOS, and SATB1 were downregulated, whereas several tumor suppressor genes such as CDKN2AIPNL, KISS1, DDIT3, TP53I13, PPARG, FOXP1 were upregulated. Data obtained through RNA-Seq further showed that N4-Eru inhibited the NOTCH/Wnt/JAK-STAT axis. This study also indicated that N4-Eru-induced apoptosis could involve several key signaling pathways in cancer. Altogether, our results suggest that N4-Eru is a promising drug to treat ALL.

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来源期刊
Epigenetics Insights
Epigenetics Insights GENETICS & HEREDITY-
CiteScore
5.10
自引率
0.00%
发文量
10
审稿时长
8 weeks
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