Reticuloendotheliosis Virus Strain T Induces miR-155, Which Targets JARID2 and Promotes Cell Survival
Reticuloendotheliosis Virus Strain T Induces miR-155, Which Targets JARID2 and Promotes Cell Survival
复制标题
DOI：
10.1128/jvi.01182-09
复制
发表时间：
2009-12-01
影响因子：
5.4
通讯作者：
Beemon, Karen L.
中科院分区：
文献类型：
--
作者：
Bolisetty, Mohan T.;Dy, George;Beemon, Karen L.
致癌微小RNA miR - 155可被多种致癌病毒上调。miR - 155的前体被称为bic，最初在禽白血病前病毒整合诱导的鸡B细胞淋巴瘤中被发现与myc协同作用。我们鉴定出另一种致癌逆转录病毒——网状内皮组织增殖病病毒T株（REV - T），它可上调鸡胚胎成纤维细胞中的miR - 155。我们还在REV - T诱导的B细胞淋巴瘤中观察到非常高的miR - 155水平。为了研究miR - 155在这些肿瘤中的作用，我们确定了JARID2 / Jumonji（一种细胞周期调节因子，是组蛋白甲基转移酶复合物的一部分）为miR - 155的一个靶标。miR - 155的过表达降低了内源性JARID2 mRNA的水平。通过检测含有JARID2 3' - 非翻译区的报告基因的抑制情况，我们证实miR - 155直接靶向人和鸡的JARID2。此外，在肿瘤细胞系中过表达与miR - 155互补的海绵结构可提高内源性JARID2 mRNA的水平。在鸡成纤维细胞中过表达JARID2导致细胞数量减少和凋亡细胞增加。miR - 155的过表达挽救了因感染B亚群禽逆转录病毒而发生细胞病变效应的细胞。因此，我们提出miR - 155具有一种促存活功能，该功能是通过下调包括JARID2在内的靶标来介导的。
The oncogenic microRNA miR-155 is upregulated by several oncogenic viruses. The precursor of miR-155, termed bic, was first observed to cooperate with myc in chicken B-cell lymphomas induced by avian leukosis proviral integrations. We identified another oncogenic retrovirus, reticuloendotheliosis virus strain T ( REV-T), that upregulates miR-155 in chicken embryo fibroblasts. We also observed very high levels of miR-155 in REV-T-induced B-cell lymphomas. To study the role of miR-155 in these tumors, we identified JARID2/Jumonji, a cell cycle regulator and part of a histone methyltransferase complex, as a target of miR-155. The overexpression of miR-155 decreased levels of endogenous JARID2 mRNA. We confirmed that miR-155 directly targets both human and chicken JARID2 by assaying the repression of reporters containing the JARID2 3'-untranslated regions. Further, the overexpression of a sponge complementary to miR-155 in a tumor cell line increased endogenous JARID2 mRNA levels. The overexpression of JARID2 in chicken fibroblasts led to decreased cell numbers and an increase in apoptotic cells. The overexpression of miR-155 rescued cells undergoing cytopathic effect caused by infection with subgroup B avian retroviruses. Therefore, we propose that miR-155 has a prosurvival function that is mediated through the downregulation of targets including JARID2.