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
{"title":"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。","authors":"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","doi":"10.1177/2516865718814543","DOIUrl":null,"url":null,"abstract":"<p><p>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. N<sup>4</sup>-Erucoyl spermidine (designed as N<sup>4</sup>-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 N<sup>4</sup>-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 <i>NDRG1, CACNA1G, TGFBR2, NOTCH1,2,3, UHRF1, DNMT1,3, HDAC1,3, KDM3A, KDM4B, KDM4C, FOS</i>, and <i>SATB1</i> were downregulated, whereas several tumor suppressor genes such as <i>CDKN2AIPNL, KISS1, DDIT3, TP53I13, PPARG, FOXP1</i> were upregulated. Data obtained through RNA-Seq further showed that N<sup>4</sup>-Eru inhibited the NOTCH/Wnt/JAK-STAT axis. This study also indicated that N<sup>4</sup>-Eru-induced apoptosis could involve several key signaling pathways in cancer. Altogether, our results suggest that N<sup>4</sup>-Eru is a promising drug to treat ALL.</p>","PeriodicalId":41996,"journal":{"name":"Epigenetics Insights","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2018-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2516865718814543","citationCount":"5","resultStr":"{\"title\":\"Identification of Deregulated Signaling Pathways in Jurkat Cells in Response to a Novel Acylspermidine Analogue-N<sup>4</sup>-Erucoyl Spermidine.\",\"authors\":\"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\",\"doi\":\"10.1177/2516865718814543\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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. N<sup>4</sup>-Erucoyl spermidine (designed as N<sup>4</sup>-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 N<sup>4</sup>-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 <i>NDRG1, CACNA1G, TGFBR2, NOTCH1,2,3, UHRF1, DNMT1,3, HDAC1,3, KDM3A, KDM4B, KDM4C, FOS</i>, and <i>SATB1</i> were downregulated, whereas several tumor suppressor genes such as <i>CDKN2AIPNL, KISS1, DDIT3, TP53I13, PPARG, FOXP1</i> were upregulated. Data obtained through RNA-Seq further showed that N<sup>4</sup>-Eru inhibited the NOTCH/Wnt/JAK-STAT axis. This study also indicated that N<sup>4</sup>-Eru-induced apoptosis could involve several key signaling pathways in cancer. Altogether, our results suggest that N<sup>4</sup>-Eru is a promising drug to treat ALL.</p>\",\"PeriodicalId\":41996,\"journal\":{\"name\":\"Epigenetics Insights\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2018-11-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1177/2516865718814543\",\"citationCount\":\"5\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Epigenetics Insights\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1177/2516865718814543\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2018/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"GENETICS & HEREDITY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Epigenetics Insights","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1177/2516865718814543","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2018/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"GENETICS & HEREDITY","Score":null,"Total":0}
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.