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Molecular signatures associated with prostate cancer cell line (PC-3) exposure to inactivated Zika virus

机译:与前列腺癌细胞系(PC-3)暴露于灭活的寨卡病毒有关的分子标记

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摘要

The recent outbreak of Zika virus (ZIKV) infection associated with microcephaly cases has elicited much research on the mechanisms involved in ZIKV-host cell interactions. It has been described that Zika virus impairs cell growth, raising a hypothesis about its oncolytic potential against cancer cells. ZIKV tumor cell growth inhibition was later confirmed for glioblastoma. It was also demonstrated that an inactivated ZIKV prototype (ZVp) based on bacterial outer membrane vesicles has antiproliferative activity upon other cancer cell lines, such as PC-3 prostate cancer cell. This study aims at understanding the pathways that might be involved with the antiproliferative effect of Zika virus against prostate cancer cells. A metabolomic approach based on high-resolution mass spectrometry analysis led to the identification of 21 statistically relevant markers of PC-3 cells treated with ZVp. The markers were associated with metabolic alterations that trigger lipid remodeling, endoplasmic reticulum stress, inflammatory mediators, as well as disrupted porphyrin and folate metabolism. These findings highlight molecular signatures of ZVp-induced response that may be involved on cellular pathways triggered by its antiproliferative effect. To our knowledge, this is the first reported metabolomic assessment of ZIKV effect on prostate cancer cells, a promising topic for further research.
机译:最近爆​​发的与小头畸形病例相关的寨卡病毒(ZIKV)感染已引起人们对ZIKV-宿主细胞相互作用涉及的机制的大量研究。已经描述了寨卡病毒损害细胞生长,提出了关于其对癌细胞的溶瘤潜力的假设。后来证实胶质母细胞瘤ZIKV肿瘤细胞生长受到抑制。还证明了基于细菌外膜囊泡的灭活的ZIKV原型(ZVp)对其他癌细胞系(例如PC-3前列腺癌细胞)具有抗增殖活性。这项研究旨在了解Zika病毒对前列腺癌细胞的抗增殖作用可能涉及的途径。基于高分辨率质谱分析的代谢组学方法导致鉴定了用ZVp处理的PC-3细胞的21种统计学相关标记。这些标记物与代谢改变有关,这些改变触发脂质重塑,内质网应激,炎症介质以及卟啉和叶酸代谢中断。这些发现突出了ZVp诱导的反应的分子标志,其可能参与了其抗增殖作用触发的细胞途径。据我们所知,这是首次报道的ZIKV对前列腺癌细胞作用的代谢组学评估,这是进一步研究的有希望的话题。

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