Bolisetty Mohan T, Dy George, Tam Wayne, Beemon Karen L
Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218, USA.
J Virol. 2009 Dec;83(23):12009-17. doi: 10.1128/JVI.01182-09. Epub 2009 Sep 16.
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.
致癌性微小RNA miR-155被多种致癌病毒上调。miR-155的前体，称为bic，最初是在禽白血病病毒整合诱导的鸡B细胞淋巴瘤中被观察到与myc协同作用。我们鉴定出另一种致癌逆转录病毒，网状内皮增生症病毒T株（REV-T），它能在鸡胚成纤维细胞中上调miR-155。我们还在REV-T诱导的B细胞淋巴瘤中观察到非常高水平的miR-155。为了研究miR-155在这些肿瘤中的作用，我们鉴定出JARID2/ Jumonji，一种细胞周期调节因子且是组蛋白甲基转移酶复合物的一部分，作为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RNA增加了内源性JARID2 mRNA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产生细胞病变效应的细胞。因此，我们提出miR-155具有通过下调包括JARID2在内的靶标介导的促生存功能。
