Putative roles as oncogene or tumour suppressor of the Mid-clustered microRNAs in Gallid alphaherpesvirus 2 (GaHV2) induced Marek's disease lymphomagenesis.
Putative roles as oncogene or tumour suppressor of the Mid-clustered microRNAs in Gallid alphaherpesvirus 2 (GaHV2) induced Marek's disease lymphomagenesis.
复制标题
中簇 microRNA 在 Gallid α疱疹病毒 2 (GaHV2) 诱导的马立克氏病淋巴瘤发生中作为癌基因或肿瘤抑制因子的假定作用
DOI：
10.1099/jgv.0.000786
复制
发表时间：
2017-05
期刊：
影响因子：
--
通讯作者：
Luo J
中科院分区：
文献类型：
--
作者：
Teng M;Yu ZH;Zhao P;Zhuang GQ;Wu ZX;Dang L;Li HZ;Ma SM;Cui ZZ;Zhang GP;Wu R;Luo J
在过去的十年中，在不同的病毒家族中发现了大量的microRNAs，特别是在疱疹病毒中。加利德甲型疱疹病毒2型(GaHV2)是一种典型的致癌性甲型疱疹病毒，可在其自然宿主中诱发快速发病的T细胞淋巴瘤，即马立克氏病(MD)。在GaHV2基因组中，有26个成熟的miRNAs，它们来自14个前体，组成了三个簇，即MEQ-簇、Mid-簇和LAT-簇。一些GaHV2 miRNAs，特别是那些在MEQ簇(例如miR-M4-5p)中的miRNAs，已经被证明在MD的发病和/或肿瘤发生中起关键作用。有趣的是，在感染的潜伏期，下游的中间簇与MEQ-簇由同一个启动子调控和转录，但这些中间簇的miRNAs在GaHV2生物学中的作用尚不清楚。我们已经在GX0101病毒中产生了中簇及其相关的单个miRNAs的缺失突变体，并证明了中簇miRNAs对病毒复制不是必需的。以GaHV2感染鸡为动物模型，我们发现，与亲本GX0101病毒相比，miR-M31的单独缺失降低了感染鸡的死亡率和肉眼肿瘤发病率，而miR-M1或miR-M11的单独缺失意外地增加了病毒的致病性或致瘤性，与整个中簇区域的缺失相似。更重要的是，我们的数据进一步证实，miR-M11-5p，即miR-M11衍生的成熟miRNA，针对病毒癌基因meq，并在GaHV2感染中抑制其表达。我们在这里报道了中间簇状miRNAs的成员miR-M31-3p和miR-M11-5p在MD淋巴肿瘤的发生中可能起癌基因或肿瘤抑制作用。
In the last decade, numerous microRNAs (miRNAs) have been identified in diverse virus families, particularly in herpesviruses. Gallid alphaherpesvirus 2 (GaHV2) is a representative oncogenic alphaherpesvirus that induces rapid-onset T-cell lymphomas in its natural hosts, namely Marek’s disease (MD). In the GaHV2 genome there are 26 mature miRNAs derived from 14 precursors assembled into three clusters, namely the Meq-cluster, Mid-cluster and LAT-cluster. Several GaHV2 miRNAs, especially those in the Meq-cluster (e.g. miR-M4-5p), have been demonstrated to be critical in MD pathogenesis and/or tumorigenesis. Interestingly the downstream Mid-cluster is regulated and transcribed by the same promoter as the Meq-cluster in the latent phase of the infection, but the role of these Mid-clustered miRNAs in GaHV2 biology remains unclear. We have generated the deletion mutants of the Mid-cluster and of its associated individual miRNAs in GX0101 virus, a very virulent GaHV2 strain, and demonstrated that the Mid-clustered miRNAs are not essential for virus replication. Using GaHV2-infected chickens as an animal model, we found that, compared with parental GX0101 virus, the individual deletion of miR-M31 decreased the mortality and gross tumour incidence of infected chickens while the deletion individually of miR-M1 or miR-M11 unexpectedly increased viral pathogenicity or oncogenicity, similarly to the deletion of the entire Mid-cluster region. More importantly, our data further confirm that miR-M11-5p, the miR-M11-derived mature miRNA, targets the viral oncogene meq and suppresses its expression in GaHV2 infection. We report here that members of the Mid-clustered miRNAs, miR-M31-3p and miR-M11-5p, potentially act either as oncogene or tumour suppressor in MD lymphomagenesis.
登录
查看更多内容
DOI：
10.1146/annurev.pathol.4.110807.092222
发表时间：
2009
期刊：
Annual review of pathology
影响因子：
--
作者：
Lee YS;Dutta A
通讯作者：
Dutta A
影响因子：
14.9
作者：
Kozomara A;Griffiths-Jones S
通讯作者：
Griffiths-Jones S
影响因子：
6.7
作者：
Kincaid RP;Sullivan CS
通讯作者：
Sullivan CS
影响因子：
14.9
作者：
Muyrers, JPP;Zhang, YM;Stewart, AF
通讯作者：
Stewart, AF
影响因子：
5.4
作者：
Burnside, Joan;Bernberg, Erin;Morgan, Robin W.
通讯作者：
Morgan, Robin W.