MiRNA-124 is a link between measles virus persistent infection and cell division of human neuroblastoma cells.
MiRNA-124 is a link between measles virus persistent infection and cell division of human neuroblastoma cells.
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DOI：
10.1371/journal.pone.0187077
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Gopas J
中科院分区：
文献类型：
--
作者：
Naaman H;Rall G;Matullo C;Veksler-Lublinsky I;Shemer-Avni Y;Gopas J
麻疹病毒（MV）感染多种淋巴和非淋巴外周器官。然而，在极少数情况下，病毒可以持续感染中枢神经系统内的细胞。尽管已知一些使MV持续存在的因素，但宿主细胞编码的microRNA（miRNA）的贡献尚未描述。miRNAs是一类转录自多细胞生物和病毒基因组的非编码RNA，以序列特异性方式调控基因表达。我们已经研究了宿主细胞编码的miRNA对人类神经母细胞瘤细胞中MV持续感染的建立的贡献。与未感染的细胞相比，持续的MV感染伴随着几种宿主细胞编码的microRNA的表达谱和水平的差异。MV持续感染人神经母细胞瘤细胞系（UKF-NB-MV），表现出高miRNA-124表达，以及细胞周期蛋白依赖性激酶6（CDK 6）（miRNA-124的已知靶点）的表达降低，导致细胞分裂较慢，但不导致细胞死亡。相比之下，UKF-NB细胞的急性MV感染没有导致miRNA-124水平增加或CDK 6减少。miRNA-124的异位过表达仅在UKF-NB-MV细胞中影响细胞活力，导致细胞死亡;这意味着miRNA-124的过表达仅在MV持续感染的情况下才能使细胞对死亡敏感。为了确定miRNA-124是否直接有助于MV持久性的建立，将过表达miRNA-124的UKF-NB细胞急性感染，导致持久感染集落的建立。我们认为，miRNA-124触发CDK 6依赖性的细胞增殖减少，这有助于在神经母细胞瘤细胞中建立MV持久性。据我们所知，这是第一个报告，以描述一个特定的miRNA在MV持久性的作用。
Measles virus (MV) infects a variety of lymphoid and non-lymphoid peripheral organs. However, in rare cases, the virus can persistently infect cells within the central nervous system. Although some of the factors that allow MV to persist are known, the contribution of host cell-encoded microRNAs (miRNA) have not been described. MiRNAs are a class of noncoding RNAs transcribed from genomes of all multicellular organisms and some viruses, which regulate gene expression in a sequence-specific manner. We have studied the contribution of host cell-encoded miRNAs to the establishment of MV persistent infection in human neuroblastoma cells. Persistent MV infection was accompanied by differences in the expression profile and levels of several host cell-encoded microRNAs as compared to uninfected cells. MV persistence infection of a human neuroblastoma cell line (UKF-NB-MV), exhibit high miRNA-124 expression, and reduced expression of cyclin dependent kinase 6 (CDK6), a known target of miRNA-124, resulting in slower cell division but not cell death. By contrast, acute MV infection of UKF-NB cells did not result in increased miRNA-124 levels or CDK6 reduction. Ectopic overexpression of miRNA-124 affected cell viability only in UKF-NB-MV cells, causing cell death; implying that miRNA-124 over expression can sensitize cells to death only in the presence of MV persistent infection. To determine if miRNA-124 directly contributes to the establishment of MV persistence, UKF-NB cells overexpressing miRNA-124 were acutely infected, resulting in establishment of persistently infected colonies. We propose that miRNA-124 triggers a CDK6-dependent decrease in cell proliferation, which facilitates the establishment of MV persistence in neuroblastoma cells. To our knowledge, this is the first report to describe the role of a specific miRNA in MV persistence.
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