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激活转录因子3对于抗肿瘤活性以及增强昂科纳酶的抗病毒特性至关重要。

Activating transcription factor 3 is crucial for antitumor activity and to strengthen the antiviral properties of Onconase.

作者信息

Vert Anna, Castro Jessica, Ribó Marc, Benito Antoni, Vilanova Maria

机构信息

Laboratori d'Enginyeria de Proteïnes, Departament de Biologia, Facultat de Ciències, Universitat de Girona, Campus de Montilivi, 17003, Girona, Spain.

Institut d'Investigació Biomèdica de Girona Josep Trueta, (IdIBGi), Girona, Spain.

出版信息

Oncotarget. 2017 Feb 14;8(7):11692-11707. doi: 10.18632/oncotarget.14302.

DOI:10.18632/oncotarget.14302
PMID:28035074
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5355296/
Abstract

Onconase is a ribonuclease that presents both antitumor and antiviral properties linked to its ribonucleolytic activity and represents a new class of RNA-damaging drugs. It has reached clinical trials for the treatment of several cancers and human papilloma virus warts. Onconase targets different RNAs in the cell cytosol but Onconase-treated cells present features that are different from a simple arrest of protein synthesis. We have used microarray-derived transcriptional profiling to identify Onconase-regulated genes in two ovarian cancer cell lines (NCI/ADR-RES and OVCAR-8). RT-qPCR analyses have confirmed the microarray findings. We have identified a network of up-regulated genes implicated in different signaling pathways that may explain the cytotoxic effects exerted by Onconase. Among these genes, activating transcription factor 3 (ATF3) plays a central role in the key events triggered by Onconase in treated cancer cells that finally lead to apoptosis. This mechanism, mediated by ATF3, is cell-type independent. Up-regulation of ATF3 may also explain the antiviral properties of this ribonuclease because this factor is involved in halting viral genome replication, keeping virus latency or preventing viral oncogenesis. Finally, Onconase-regulated genes are different from those affected by nuclear-directed ribonucleases.

摘要

昂科纳酶是一种核糖核酸酶，具有与其核糖核酸水解活性相关的抗肿瘤和抗病毒特性，代表了一类新型的RNA损伤药物。它已进入治疗多种癌症和人乳头瘤病毒疣的临床试验阶段。昂科纳酶作用于细胞质中的不同RNA，但经昂科纳酶处理的细胞呈现出的特征不同于简单的蛋白质合成停滞。我们利用微阵列转录谱分析来鉴定两种卵巢癌细胞系（NCI/ADR-RES和OVCAR-8）中受昂科纳酶调控的基因。RT-qPCR分析证实了微阵列分析的结果。我们鉴定出了一个上调基因网络，这些基因涉及不同的信号通路，这可能解释了昂科纳酶所发挥的细胞毒性作用。在这些基因中，激活转录因子3（ATF3）在经昂科纳酶处理的癌细胞中引发的最终导致细胞凋亡的关键事件中起核心作用。由ATF3介导的这一机制不依赖于细胞类型。ATF3的上调也可能解释了这种核糖核酸酶的抗病毒特性，因为该因子参与阻止病毒基因组复制、维持病毒潜伏状态或预防病毒致癌作用。最后，昂科纳酶调控的基因不同于受核导向核糖核酸酶影响的基因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbf2/5355296/3cd7692a3cc2/oncotarget-08-11692-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbf2/5355296/7261154ee2af/oncotarget-08-11692-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbf2/5355296/a4023698387d/oncotarget-08-11692-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbf2/5355296/3cd7692a3cc2/oncotarget-08-11692-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbf2/5355296/7261154ee2af/oncotarget-08-11692-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbf2/5355296/a4023698387d/oncotarget-08-11692-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dbf2/5355296/3cd7692a3cc2/oncotarget-08-11692-g003.jpg

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3
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4
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