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鸡马立克氏病中长链非编码RNA的保守性与特征

The conservation and signatures of lincRNAs in Marek's disease of chicken.

作者信息

He Yanghua, Ding Yi, Zhan Fei, Zhang Huanmin, Han Bo, Hu Gangqing, Zhao Keji, Yang Ning, Yu Ying, Mao Li, Song Jiuzhou

机构信息

Department of Animal &Avian Sciences, University of Maryland, College Park, MD 20742, USA.

USDA, Agricultural Research Service, Avian Disease and Oncology Laboratory, East Lansing, MI 48823, USA.

出版信息

Sci Rep. 2015 Oct 16;5:15184. doi: 10.1038/srep15184.

Abstract

Long intergenic non-coding RNAs (lincRNAs) associated with a number of cancers and other diseases have been identified in mammals, but they are still formidable to be comprehensively identified and characterized. Marek's disease (MD) is a T cell lymphoma of chickens induced by Marek's disease virus (MDV). Here, we used a MD chicken model to develop a precise pipeline for identifying lincRNAs and to determine the roles of lincRNAs in T cell tumorigenesis. More than 1,000 lincRNA loci were identified in chicken bursa. Computational analyses demonstrated that lincRNAs are conserved among different species such as human, mouse and chicken. The putative lincRNAs were found to be associated with a wide range of biological functions including immune responses. Interestingly, we observed distinct lincRNA expression signatures in bursa between MD resistant and susceptible lines of chickens. One of the candidate lincRNAs, termed linc-satb1, was found to play a crucial role in MD immune response by regulating a nearby protein-coding gene SATB1. Thus, our results manifested that lincRNAs may exert considerable influence on MDV-induced T cell tumorigenesis and provide a rich resource for hypothesis-driven functional studies to reveal genetic mechanisms underlying susceptibility to tumorigenesis.

摘要

在哺乳动物中已经鉴定出与多种癌症和其他疾病相关的长链基因间非编码RNA(lincRNA),但要全面鉴定和表征它们仍然具有很大难度。马立克氏病(MD)是由马立克氏病病毒(MDV)诱发的鸡T细胞淋巴瘤。在此,我们利用MD鸡模型开发了一种精确的流程来鉴定lincRNA,并确定lincRNA在T细胞肿瘤发生中的作用。在鸡法氏囊中鉴定出了1000多个lincRNA基因座。计算分析表明,lincRNA在人类、小鼠和鸡等不同物种中具有保守性。推定的lincRNA被发现与包括免疫反应在内的广泛生物学功能相关。有趣的是,我们在MD抗性和易感品系鸡的法氏囊中观察到了不同的lincRNA表达特征。其中一个候选lincRNA,称为linc-satb1,被发现通过调控附近的蛋白质编码基因SATB1在MD免疫反应中发挥关键作用。因此,我们的结果表明lincRNA可能对MDV诱导的T细胞肿瘤发生产生相当大的影响,并为基于假设的功能研究提供了丰富资源,以揭示肿瘤发生易感性的遗传机制。

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