MicroRNA-26a-mediated regulation of interleukin-2 expression in transformed avian lymphocyte lines.
MicroRNA-26a-mediated regulation of interleukin-2 expression in transformed avian lymphocyte lines.
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DOI：
10.1186/1475-2867-10-15
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发表时间：
2010-05-04
影响因子：
5.8
通讯作者：
Nair V
中科院分区：
文献类型：
--
作者：
Xu H;Yao Y;Smith LP;Nair V
微rna （mi）是一类小的非编码rna，在诱导各种癌症（包括致癌病毒诱导的淋巴瘤）中发挥关键作用。虽然一些mirna是致癌的，但mirna如miR-26a在许多癌症中一直下调，这表明它们具有潜在的肿瘤抑制功能。许多病毒转化的禽淋巴瘤细胞系的全球miRNA表达谱显示gga-miR-26a表达下调，与转化的分子机制或病毒病因无关。许多病毒对淋巴细胞的肿瘤转化伴随着高水平的增殖反应，主要通过细胞因子如IL-2介导。鸡IL-2在体外和体内可以调节t细胞增殖和细胞毒性，在白血病等疾病中观察到IL-2表达失调。gga-miR-26a在马雷克氏病病毒（MDV）、禽白血病病毒（ALV）和网状内皮增生病毒（REV）转化的鸡淋巴瘤细胞中的表达水平与正常淋巴细胞相比持续下调。无论病毒病因和转化的分子机制如何，miR-26a的下调与该miRNA的肿瘤抑制作用是一致的。尽管这在癌症中已经确立了作用，但我们通过报告基因和生化分析证明了该miRNA在直接靶向鸡IL-2中的额外作用。下调miR-26a可解除该miRNA对IL-2表达的抑制作用。我们发现miR-26a在许多禽淋巴瘤细胞中全局下调，无论其转化机制如何，这重申了该miRNA高度保守的肿瘤抑制功能。然而，由于具有直接靶向鸡IL-2的潜力，这些肿瘤细胞中miR-26a的下调可以减轻对IL-2表达的抑制作用，有助于转化淋巴细胞系的增殖特征。
Micro(mi)RNAs are a class of small non-coding RNAs that play critical roles in the induction of various cancers, including lymphomas induced by oncogenic viruses. While some of the miRNAs are oncogenic, miRNAs such as miR-26a are consistently downregulated in a number of cancers, demonstrating their potential tumor suppressor functions. Global miRNA expression profiles of a number of virus-transformed avian lymphoma cell lines have shown downregulation of gga-miR-26a expression, irrespective of molecular mechanisms of transformation or the viral aetiology. The neoplastic transformation of lymphocytes by many viruses accompanies high levels of proliferative responses, mostly mediated through cytokines such as IL-2. Chicken IL-2 can modulate T-cell proliferation and cytotoxicity in vitro and in vivo and dysregulation of IL-2 expression is observed in diseases such as leukaemia. The expression levels of gga-miR-26a in chicken lymphoma cells transformed by 3 distinct avian oncogenic viruses, viz Marek's disease virus (MDV), avian leukosis virus (ALV) and Reticuloendotheliosis virus (REV) were consistently downregulated compared to the levels in the normal lymphocytes. This downregulation of miR-26a regardless of the viral etiology and molecular mechanisms of transformation was consistent with the tumor suppressor role of this miRNA. Notwithstanding this well-established role in cancer, we demonstrate the additional role of this miRNA in directly targeting chicken IL-2 through reporter and biochemical assays. The downregulation of miR-26a can relieve the suppressive effect of this miRNA on IL-2 expression. We show that miR-26a is globally downregulated in a number of avian lymphoma cells irrespective of the mechanisms of transformation, reiterating the highly conserved tumor suppressor function of this miRNA. However, with the potential for directly targeting chicken IL-2, the downregulation of miR-26a in these tumor cells could relieve the inhibitory effect on IL-2 expression assisting in the proliferative features of the transformed lymphocyte lines.
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DOI：
10.1038/nri2580
发表时间：
2009-07
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
8
作者：
Visone, R.;Pallante, P.;Fusco, A.
通讯作者：
Fusco, A.
影响因子：
4.4
作者：
Wang, Jun;Lee, Seungsoo;Shannon, M. Frances
通讯作者：
Shannon, M. Frances
影响因子：
11.5
作者：
Bandres, Eva;Bitarte, Nerea;Garcia-Foncillas, Jesus
通讯作者：
Garcia-Foncillas, Jesus
影响因子：
10.5
作者：
Huse, Jason T.;Brennan, Cameron;Holland, Eric C.
通讯作者：
Holland, Eric C.